bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER) 2.0 QUERI: study protocol for a cluster-randomized hybrid type 3 effectiveness-implementation trial
Authors: Hamilton Alison B. , Finley Erin P. , Bean-Mayberry Bevanne , Lang Ariel , Haskell Sally G. , Moin Tannaz , Farmer Melissa M. ,   the EMPOWER QUERI Team
Published: March 2023

Background

Women Veterans are the fastest-growing segment of Veterans Health Administration (VA) users. The VA has invested heavily in delivering care for women Veterans that is effective, comprehensive, and gender-tailored. However, gender disparities persist in cardiovascular (CV) and diabetes risk factor control, and the rate of perinatal depression among women Veterans is higher than that among civilian women. Challenges such as distance, rurality, negative perception of VA, discrimination (e.g., toward sexual and/or gender minority individuals), and harassment on VA grounds can further impede women’s regular use of VA care. Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER) 2.0 builds on work to date by expanding access to evidence-based, telehealth preventive and mental health services for women Veterans with high-priority health conditions in rural and urban-isolation areas.

Methods

EMPOWER 2.0 will evaluate two implementation strategies, Replicating Effective Practices (REP) and Evidence-Based Quality Improvement (EBQI), in supporting the implementation and sustainment of three evidence-based interventions (Virtual Diabetes Prevention Program; Telephone Lifestyle Coaching Program; and Reach Out, Stay Strong Essentials) focused on preventive and mental health care for women Veterans. We will conduct a mixed-methods implementation evaluation using a cluster-randomized hybrid type 3 effectiveness-implementation trial design to compare the effectiveness of REP and EBQI on improved access to and rates of engagement in telehealth preventive lifestyle and mental health services. Other outcomes of interest include (a) VA performance metrics for telehealth care delivery and related clinical outcomes; (b) progression along the Stages of Implementation Completion; (c) adaptation, sensemaking, and experiences of implementation among multilevel stakeholders; and (d) cost and return on investment. We will also generate implementation playbooks for program partners to support scale-up and spread of these and future evidence-based women’s health programs and policies.

Discussion

EMPOWER 2.0 provides a model for mixed-methods hybrid type 3 effectiveness-implementation trial design incorporating evaluation of performance metrics, implementation progress, stakeholder experience, and cost and return on investment, with the ultimate goal of improving access to evidence-based preventive and mental telehealth services for women Veterans with high-priority health conditions.

Trial registration

ClinicalTrials.gov, NCT05050266. Registered on 20 September 2021.
Prevalence and associated risk factors of gastrointestinal helminths and coccidian infections in domestic goats, Capra hircus, in Minya, Egypt
Authors: Mohamed Hend Ibrahim , Arafa Waleed M. , El-Dakhly Khaled Mohamed
Published: March 2023

Background

Helminth and coccidian infections are among potential parasitic infections in the livestock production. The present study aimed to determine the prevalence and intensity of gastrointestinal helminths as well asEimeiaspecies in domestic goats.

Results

The overall prevalence of parasitic infections was 50.24% (206/410). Twenty two species of helminth eggs/Eimeriaspp. oocysts were revealed. The prevalence of helminths was 21.95% (90/410) and that ofEimeriaspp. was 39.27% (161/410). Mixed infection was reported in 10.98% (45/410). The highest prevalence was found in young animals (75.0%; 60/80) followed by yearlings (58.46%; 76/130) and the lowest one was in adults (35.0%; 70/200). The infection rate was higher in females (59.02%; 180/305) than males (24.76%; 26/105). The prevalence was mostly highest in summer (63.85%; 83/130) followed by winter (57.78%; 52/90), autumn (40.0%; 28/70) and the lowest one was in spring (35.83%; 43/120). Age, sex and seasonal variations revealed significant (P ≤ 0.05) differences among examined goats. The infection with both nematodes andEimeriaspp. were detected in 7.32% (30/410). The co-infection withEimeriaspp. and tapeworms were found in 2.93% (12/410). Both trematodes andEimeriaspp. were seen in 0.73% (3/410) of examined specimens. NineEimeriaspecies were recorded;Eimeria ninakohlyakim-ovae,E. hirci,E.caprinova,E. caprina,E. christenseni,E. jolchijevi,E. arloingi, E. apsheronicaandE. alijevi. The most predominantEimeriaspecies wasE. arloingi(23.17%; 95/410) and the least abundant one wasE. apsheronica(0.73%; 3/410). The revealed trematodes wereFasciolaspp. (0.49%) andParamphistomumspp. (0.24%). Among cestodes, tapeworms belonged to Anoplocephalids includedMonieziaspp. (7.31%) andAvitellinasp. (0.49%) were detected. Meanwhile, coproculture revealed that the prevalence of nematodes infection was 13.41% (55/410) including nine species;Chabertia ovina,Ostertagia ostertagi,Haemonchus contortus,Trichostrongylus axei,T. colubriformis,Bunostomumsp.,Cooperia oncophora,Cooperia curticeiandStrongyloidesspp.

Conclusion

In the present study, the prevalence of helminths was 21.95% and that ofEimeriaspp. was 39.27%, which is considered a high infection rate. Accordingly Strict hygienic measures as well as regular deworming are highly recommended to avoid wide spread of both helminth and coccidial infections.
Clinicopathologic Features of Breast Cancer in Egypt—Contemporary Profile and Future Needs: A Systematic Review and Meta-Analysis
Authors: Azim Hamdy A. , Elghazawy Hagar , Ghazy Ramy M. , Abdelaziz Ahmed H. , Abdelsalam Marwa , Elzorkany Amira , Kassem Loay
Published: March 2023

PURPOSE

Breast cancer (BC) is the most common cancer among Egyptian females. No current national cancer database is available in Egypt to provide reliable data on the specific clinicopathologic features of BC in this population. Herein, we investigated the clinical profile of BC among Egyptian women.

METHODS

A systematic review of studies on BC published from inception until December 2021 was performed. We explored pooled estimated proportions of different stages of BC at presentation in Egypt and other clinicopathologic features including age, menopausal status, tumor (T) and lymph node (N) stages, and biological subtypes. Data analysis was performed using meta package (R).

RESULTS

Twenty-six studies were eligible for our systematic review and meta-analysis, including 31,172 BC cases. In 12 studies, including 15,067 patients with BC, the estimated mean age was 50.46 years (95% CI, 48.7 to 52.1; I2, 99%), with a pooled proportion of premenopausal/perimenopausal women of 57% (95% CI, 50 to 63; I2, 98%). Among 9,738 patients with BC, pooled proportions of stage I, II, III, and IV were 6% (95% CI, 4 to 8; I2, 90%), 37% (95% CI, 31 to 43; I2, 93%), 45% (95% CI, 42 to 49; I2, 78%), and 11% (95% CI, 9 to 15; I2, 87%), respectively. The pooled proportions of patients with T3 and T4 tumors were 21% (95% CI, 14 to 31; I2, 99%) and 8% (95% CI, 5 to 12; I2, 96%), respectively, while those with positive lymph nodes were 70% (95% CI, 59 to 79; I2, 99%).

CONCLUSION

Dominance of advanced stage and young age at diagnosis represented the two main features of BC among Egyptian women. Our data may serve to guide the policymakers in Egypt as well as other countries with lower resources to prioritize the diagnostic and therapeutic needs in this context.
Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study
Authors: Sallman David A. , Al Malki Monzr M. , Asch Adam S. , Wang Eunice S. , Jurcic Joseph G. , Bradley Terrence J. , Flinn Ian W. , Pollyea Daniel A. , Kambhampati Suman , Tanaka Tiffany N. , Zeidner Joshua F. , Garcia-Manero Guillermo , Jeyakumar Deepa , Komrokji Rami , Lancet Jeffrey , Kantarjian Hagop M. , Gu Lin , Zhang Yajia , Tan Anderson , Chao Mark , O'Hear Carol , Ramsingh Giridharan , Lal Indu , Vyas Paresh , Daver Naval G.
Published: March 2023

PURPOSE

Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479 ).

PATIENTS AND METHODS

Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once‐weekly or once‐every-2-week maintenance dose. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and complete remission (CR) rate.

RESULTS

Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was −0.7 g/dL (range, −3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS.

CONCLUSION

Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).
Undergraduate Anesthesia Skills for a Global Surgery Agenda: Students’ Self-Reported Competence
Authors: Spijkerman Sandra , Manning Dianne Mary , Green-Thompson Lionel Patrick
Published: March 2023

BACKGROUND:

Safe anesthesia is imperative for the Global Surgery agenda and Sustainable Development Goal 3. Due to a shortage of specialists in South Africa (SA), anesthetic services are often provided by nonspecialist doctors, often newly qualified and frequently without immediate supervision. The burden of disease in the developing world demands fit-for-purpose, day-one medical graduates. Although undergraduate anesthesia training is mandatory for medical students in SA, no outcomes are specified, and these are decided autonomously at each medical school. This study describes the current self-perceived anesthetic competence of medical students in SA as a needs assessment directed at achieving the goals of Global Surgery in SA and other developing countries.

METHODS:

In this cross-sectional observational study, 1689 students (89% participation rate), representing all medical schools in SA, rated their self-perceived competence at graduation in 54 anesthetic-related Likert scale items in 5 themes: patient evaluation, patient preparation for anesthesia, practical skills performance, administration of anesthesia, and the management of intraoperative complications. Medical schools were divided into clusters A (≥25 days of anesthetic training) and B (<25 days). Descriptive statistics, Fisher exact test, and a mixed-effects regression model were used in the statistical analysis.

RESULTS:

Students felt more prepared for history-taking and patient examination than for managing emergencies and complications. The self-perceived competence of students at cluster A schools was higher across all 54 items and all 5 themes. The same was observed for general medical skills and skills relating to maternal mortality in SA.

CONCLUSIONS:

Time-on-task, capacity for repetition, and student maturity might have impacted self-efficacy and should be considered in curriculum development. Students felt less prepared for emergencies. Focused training and assessment aimed at emergency management should be considered. Students did not feel competent in general medical areas, in which anesthetists are experts, including resuscitation, fluid management, and analgesia. Anesthetists should take ownership of this training at the undergraduate level. Cesarean delivery is the most performed surgical procedure in sub-Saharan Africa. The Essential Steps in Managing Obstetric Emergencies (ESMOE) program was designed for internship training but can be introduced at undergraduate level. This study suggests that curriculum reform is required. The achievement of an agreed-upon set of standardized national undergraduate anesthetic competencies may ensure fit-for-purpose practitioners. Undergraduate and internship training should align to form part of a continuum of basic anesthetics training in SA. The findings of this study might benefit curriculum development in other regions with similar contexts.
Did God WriteMoby-Dick?
Authors: Coviello Peter
Published: March 2023

This essay takes up two conceptual formations of great consequence to Herman Melville: “religion” and “literature.” Part of what binds them so tightly for Melville is a set of transformative upheavals in liberal culture that we have lately come to know by a different name: “secularism.” Melville helps us think secularism not as the extirpation of religion in modernity but as an ensemble of broadly disciplinary interventions, whose aim was both to exalt Protestant Christianity as the authorizing sign for planetary white dominion and to demote theology itself into a practice of gentle suasion, private consciousness-raising, influence. Moby-Dick is a novel shouting not into the void of a world abandoned by God—or not only—but into the empty space where the theocratic authority of the pulpit once was, where words fired by the titanic power of Godliness itself narrated, shaped, made history. In his fury and his despair, Melville maps out in cartographic detail the solidification of what would become “literature” as such as a by-product of secular discipline.
Reading Christian Experience
Authors: Mason Emma
Published: March 2023

The radicalism of Christianity is often underplayed in literary studies by scholars who perceive its theology as politically suspect and inflexible. Yet an unwillingness to engage with Christian theology and experience produces critical misreadings of literary texts that reveal Christianity’s doctrines and ideas as anything but myopic. This essay explores the doctrine of kenosis as integral to Christianity’s compassionate vision in the work of two writers associated with the nineteenth-century Catholic revival: Christina Rossetti and Gerard Manley Hopkins. Kenosis describes Christ’s becoming human as a temporary letting go of his divinity; for Rossetti and Hopkins, this models a way of being and thinking in which the subject is untied from an ego desirous of control and power. Both writers consequently embraced the interdependence of the Father, Son, and Holy Spirit in the Trinity as a way of conceptualizing faith through shared humility and weakness. This approach to the self, the world, and God is an important one to identify in Christian texts, but it also exemplifies a Christian way of thinking more broadly attuned to the depiction of vulnerability and introspection in literature and culture.
Design of velocity sensor for robotic fish based on fiber Bragg grating
Authors: Xie Shuhang , Xu Dong , Dong Junjun , Dai Wei
Published: March 2023

The artificial lateral lines of robotic fish (a kind of underwater unmanned vehicle) have been studied extensively, but mostly based on pressure measurements. Based on fiber Bragg grating, a kind of sensor for artificial lateral line of robotic fish is proposed in this paper. This sensor structure is sensitive to flow velocity. The sensor adopts the target-type structure, and the target is the impacted end of the water flow, so the target arm is deformed. The strain of the target arm is measured by the fiber Bragg grating, so as to reflect the impact of water flow at different flow velocities on the target. The experimental data show that there is an obvious linear relationship between the central wavelength offset and the square of the velocity. Our work demonstrates the feasibility of this sensor structure for velocity measurements.
Meta-analysis of the prevalence of Carpal Tunnel Syndrome (CTS) among dental health care personnel
Authors: Chenna Deepika , Madi Medhini , Kumar Mathangi , Kumar Vijay , Chopperla Sitaram , Tadikonda Abhinav , Pentapati Kalyana
Published: March 2023

Background: Carpal Tunnel Syndrome (CTS) is one such common disorder among dental health care personnel caused due to the entrapment neuropathy of the median nerve in the carpal tunnel. We aimed to evaluate the pooled estimates of the CTS among dental healthcare personnel.

Methods: We systematically reviewed the existing literature from six databases till January 1st, 2022. Studies reported in English along with the prevalence of CTS or where prevalence could be calculated were included. Independent screening of title and abstracts, and the full text was done by two examiners. Information collected was authors, year of publication, geographic location, type of dental healthcare personnel, sample size, distribution of age, sex, CTS, method of diagnosis, and risk of bias. The random effect model was used to estimate the pooled estimates.

Results: Thirty-seven studies yielded 38 estimates. A total of 17,152 dental health care personnel were included of which 2717 had CTS. The overall pooled prevalence of CTS among the included studies was 15%, with a high heterogeneity. Meta-analysis showed no significant difference in the pooled estimates of CTS between male and female dental healthcare personnel (OR: 0.73; 95% CI: 0.52 -1.02; I2= 69.71). The pooled estimates among the dentist and dental auxiliaries were 20% and 10%, respectively. The pooled prevalence of CTS with self-reported measures, clinical examination and NCS were 21%, 13% and 8% respectively. Meta-regression showed that the prevalence estimates were significantly associated with publication year (coefficient: 0.006; 95% CI= 0.002-0.01).

Conclusion: One out of seven dental health care personnel may be affected by CTS. No significant difference was seen in the prevalence of CTS between male and female dental healthcare personnel.
Nanopore sequencing of DNA barcodes to unveil the diversity of fungal mock communities
Authors: Pedroso-Roussado Cristiano , Guppy Fergus , Bowler Lucas , Inacio Joao
Published: March 2023

Background: The fungal component of the gut microbiome has been underrepresented in most gut microbiome studies. While next-generation sequencing (NGS) approaches have been used to assess the diversity and role of the gut mycobiome, differences in experimental design and downstream analyses may induce bias and differential outcomes. This study assessed the capacity of nanopore sequencing to retrieve the microbial profile and relative abundance of a mock fungal community comprised of Candida glabrata, Meyerozyma guilliermondii, Pichia kudriavzevii, Clavispora lusitaniae and Candida parapsilosis.

Methods: The approach was implemented using the MinION system and involved the analysis of sequencing libraries made from equimolar mixtures of the PCR-amplified internal transcriber spacer genomic regions of the target species.

Results: Nanopore sequencing successfully retrieved the composition of the fungal mock community in terms of the different taxa present. However, the approach was unable to correctly assess the expected relative abundances of each species in the same community, showing some yet undetermined bias that may be related to the size of the respective target DNA fragments. Clavispora lusitaniae was consistently overrepresented in the mixtures, while C. glabrata was underrepresented. The remaining three species showed relative abundances more aligned with the expected values of an equimolar mixture.

Conclusions: Although not yielding the expected results for the relative abundances, the values obtained from independent sequencing runs were similar for all species, suggesting a good reliability but questionable accuracy in this sequencing approach.
Tuva Destanlarında Hiperbol (Mübalağa) Kullanımı Üzerine
Authors: ARÇIN Salih Mehmet
Published: March 2023

Hiperbol (Abartı / Mübalağa) söylemde en genel ifadeyle bir şeyi olduğundan daha iyi, daha çarpıcı bir şekilde konuşma veya yazmanın yolu olarak tanımlanabilir. Bu çalışmada öncelikle hiperbol kavramı ve kavramın alanyazındaki farklı biçimleri hakkında bilgi verilmiş, kavramın Batı’da hem teorik ve edebî bağlamlarda hem de derlem tabanlı çalışmalar üzerinde kullanımının teorik boyutları tanıtılmaya çalışılmıştır. Bu bağlamda elde edilen veriler çerçevesinde Tuva kahramanlık destanları analiz edilmiştir. Araştırma nesnesi olarak seçilen Tuva kahramanlık destanlarına ait bir derlem mevcut olmadığı için Türkiye Türkçesine aktarılmış olan Ergun - Aça (2004), Tıva Kahramanlık Destanları I; Ergun - Aça (2005), Tıva Kahramanlık Destanları II; Arıkoğlu - Borbaanay (2007), Tuva Destanları; Arçın (2014), Tuva Destanları 2: Haan-Tögüldür metinlerinden örnekleme yöntemi ile veri toplanmıştır. Bu açıdan çalışmada nitel bir yöntem uygulanmıştır.

Çalışmada, Batı’daki hiperbol yaklaşımlarının modellemelerine alternatif olarak Türkçenin yapısına uygun bir model önerilmektedir. Sonuç olarak, hiperboller Tuva Türkçesi destan metinlerindeki verilere göre Türkçenin genel yapısına uygun bir biçimde varyasyonları ile ortaya konulmuş ve 4 başlık adı altında örneklendirilmiştir: 1. Nesnel Hiperboller 2. Nicel Hiperboller 3. Nitel Hiperboller 4. Belirteç Hiperboller.
Plesiobiotic Associations Between Ants: A Common Yet Underreported Phenomenon in the Mediterranean Region?
Authors: Schifani Enrico , Alicata Antonio
Published: March 2023

Among ants, plesiobiotic associations are defined as occasional or regular nesting of heterospecific colonies in close proximity and without any biological interdependence. Habitats with a scarcity of available nesting microhabitats and ecological dissimilarity between the involved species are supposed to favor the frequency of plesiobiosis. In the last review published on this topic, the authors summarized all the plesiobiotic species pairs reported in the literature for the Holarctic region, listing 48 species pairs. On the basis of our field investigation in the Mediterranean island of Sicily (Italy), we are able to report additional 81 plesiobiotic ant-ant species pairs, two associations of three ant species, and four ant-termite pair associations. We suggest plesiobiosis to be severely underreported rather than rare, at least in the Mediterranean region.
Multi-wavelength transponders for high-capacity optical networks: a physical-layer-aware network planning study
Authors: Müller Jasper , Jovanovic Ognjen , Fehenberger Tobias , Di Rosa Gabriele , Elbers Jörg-Peter , Mas-Machuca Carmen
Published: March 2023

Continued cost- and power-efficient capacity scaling in optical networks is imperative to keep pace with ever-increasing traffic demands. In this paper, we investigate multi-wavelength transponders as a potential way forward. Suitable system architectures and realistic specifications of multi-wavelength transponders are identified and analyzed in terms of transmit optical signal-to-noise ratio penalties and spectral constraints. We investigate the performance for different specifications as compared to single-wavelength transponders in a network planning study on two network topologies, developing guidelines for multi-wavelength transponder specifications and their potential benefits. The studies show a reduction in the number of required lasers of up to 83% at the expense of a slight increase in the number of lightpaths, demonstrating the potential for significant cost savings and efficiency improvements.
Tailored-edge Glass Cleaving with Ultrafast Lasers
Authors: Kaiser Myriam , Ede Svenja , Kleiner Jonas , Kahmann Max , Flamm Daniel
Published: March 2023

The laser-based fabrication of glass contours with tailored edges is reported. To achieve energy deposition along arbitrary edge geometries, holographic beam splitters are applied. After laser modification, chemical, mechanical, and thermal separation processes are considered.
High stability fiber amplifiers for terrestrial and space sensing applications at 1 and 2 µm
Authors: Baer Patrick , Cebeci Pelin , Giesberts Martin , Hoffmann Dieter
Published: March 2023

Fraunhofer ILT develops low-linewidth, high-stability ytterbium-, thulium- and holmium-doped fiber amplifiers e.g. for pre studies of gravitational wave detectors in the context of the LISA and the ETEST project. Here, we give an overview on our 1 µm and 2 µm fiber amplifier development for use in space and on earth.
Revolutionary Optical Beam Steering
Authors: McManamon Paul
Published: March 2023

We have developed mechanical and non-mechanical beam steering technologies that will change the way optical systems are built. We can provide a very compact way rapidly steer multiple beams through almost any size aperture.
Confocal probe based on the second harmonic generation for measurement of linear and angular displacements
Authors: Sato Ryo , Shimizu Yuki , Shimizu Hiroki , Matsukuma Hiraku , Gao Wei
Published: March 2023

A measurement method based on a confocal probe on the second harmonic generation that can measure linear and angular displacements in the focusing point is proposed. In the proposed method, a pinhole or an optical fiber placed in front of the detector in conventional confocal probes is replaced by a nonlinear optical crystal, which is utilized as a medium generating second harmonic wave whose light intensity changes by the linear and angular displacements of a target under measurement. The feasibility of the proposed method is verified by theoretical calculations and experiments with the newly designed optical setup. Experimental results have demonstrated that the developed confocal probe has a resolution of 20 nm and 5 arc-seconds for measurement of linear and angular displacements, respectively.
The N-terminal extension of Arabidopsis ARGONAUTE 1 is essential for microRNA activities
Authors: Xu Ye , Zhang Yong , Li Zhenfang , Soloria Alyssa K. , Potter Savannah , Chen Xuemei
Published: March 2023

microRNAs (miRNAs) regulate target gene expression through their ARGONAUTE (AGO) effector protein, mainly AGO1 inArabidopsis thaliana. In addition to the highly conserved N, PAZ, MID and PIWI domains with known roles in RNA silencing, AGO1 contains a long, unstructured N-terminal extension (NTE) of little-known function. Here, we show that the NTE is indispensable for the functions of Arabidopsis AGO1, as a lack of the NTE leads to seedling lethality. Within the NTE, the region containing amino acids (a.a.) 91 to 189 is essential for rescuing anago1null mutant. Through global analyses of small RNAs, AGO1-associated small RNAs, and miRNA target gene expression, we show that the region containing a.a. 91–189 is required for the loading of miRNAs into AGO1. Moreover, we show that reduced nuclear partitioning of AGO1 did not affect its profiles of miRNA and ta-siRNA association. Furthermore, we show that the 1-to-90a.a. and 91-to-189a.a. regions of the NTE redundantly promote the activities of AGO1 in the biogenesis of trans-acting siRNAs. Together, we report novel roles of the NTE of Arabidopsis AGO1.
Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project
Authors: Mukumbwa-Mwenechanya Mpande , Mubiana Muhau , Somwe Paul , Zyambo Khozya , Simwenda Maureen , Zongwe Nancy , Kalunkumya Estella , Mwango Linah Kampilimba , Rabkin Miriam , Mpesela Felton , Chungu Fred , Mwanza Felix , Preko Peter , Bolton-Moore Carolyn , Bosomprah Samuel , Sharma Anjali , Morton Khunga , Kasonde Prisca , Mulenga Lloyd , Lingu Patrick , Mulenga Priscilla Lumano
Published: March 2023

Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3–6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1–5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher’s exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.
Different clinical features in Malawian outpatients presenting with COVID-19 prior to and during Omicron variant dominance: A prospective observational study
Authors: Chibwana Marah G. , Thole Herbert W. , Anscombe Cat , Ashton Philip M. , Green Edward , Barnes Kayla G. , Cornick Jen , Turner Ann , Witte Desiree , Nthala Sharon , Thom Chikondi , Kanyandula Felistas , Ainani Anna , Mtike Natasha , Tambala Hope , N’goma Veronica , Mwafulirwa Dorah , Asima Erick , Morton Ben , Gmeiner Markus , Gundah Zaziwe , Kawalazira Gift , French Neil , Feasey Nicholas , Heyderman Robert S. , Swarthout Todd D. , Jambo Kondwani C.
Published: March 2023

The SARS-CoV-2 Omicron variant has resulted in a high number of cases, but a relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants. Therefore, we assessed the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population. We collected data from outpatients presenting at two primary healthcare facilities in Blantyre, Malawi, from November 2020 to March 2022. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19, from whom we collected nasopharyngeal swabs for SARS-CoV-2 PCR testing, and sequenced positive samples to identify infecting-variants. In addition, we calculated the risk of presenting with a given symptom in individuals testing SARS-CoV-2 PCR positive before and during the Omicron variant-dominated period. Among 5176 participants, 6.4% were under 5, and 77% were aged 18 to 50 years. SARS-CoV-2 infection prevalence peaked in January 2021 (Beta), July 2021 (Delta), and December 2021 (Omicron). We found that cough (risk ratio (RR), 1.50; 95% confidence interval (CI), 1.00 to 2.30), fatigue (RR 2.27; 95% CI, 1.29 to 3.86) and headache (RR 1.64; 95% CI, 1.15 to 2.34) were associated with a high risk of SARS-CoV-2 infection during the pre-Omicron period. In comparison, only headache (RR 1.41; 95% CI, 1.07 to 1.86) did associate with a high risk of SARS-CoV-2 infection during the Omicron-dominated period. In conclusion, clinical symptoms associated with Omicron infection differed from prior variants and were harder to identify clinically with current symptom guidelines. Our findings encourage regular review of case definitions and testing policies to ensure case ascertainment.
The effects of social determinants on children’s health outcomes in Bangladesh slums through an intersectionality lens: An application of multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)
Authors: Barua Proloy , Kibuchi Eliud , Aktar Bachera , Chowdhury Sabrina Fatema , Mithu Imran Hossain , Quayyum Zahidul , Filha Noemia Teixeira de Siqueira , Leyland Alastair H. , Rashid Sabina Faiz , Gray Linsay
Published: March 2023

Empirical evidence suggests that the health outcomes of children living in slums are poorer than those living in non-slums and other urban areas. Improving health especially among children under five years old (U5y) living in slums, requires a better understanding of the social determinants of health (SDoH) that drive their health outcomes. Therefore, we aim to investigate how SDoH collectively affects health outcomes of U5y living in Bangladesh slums through an intersectionality lens. We used data from the most recent national Urban Health Survey (UHS) 2013 covering urban populations in Dhaka, Chittagong, Khulna, Rajshahi, Barisal, Sylhet, and Rangpur divisions. We applied multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) to estimate the Discriminatory Accuracy (DA) of the intersectional effects estimates using Variance Partition Coefficient (VPC) and the Area Under the Receiver Operating Characteristic Curve (AUC-ROC). We also assessed the Proportional Change in Variance (PCV) to calculate intersectional effects. We considered three health outcomes: cough, fever, and acute respiratory infections (ARI) in U5y.We found a low DA for cough (VPC = 0.77%, AUC-ROC = 61.90%), fever (VPC = 0.87%, AUC-ROC = 61.89%) and ARI (VPC = 1.32%, AUC-ROC = 66.36%) of intersectional strata suggesting that SDoH considered do not collectively differentiate U5y with a health outcome from those with and without a health outcome. The PCV for cough (85.90%), fever (78.42%) and ARI (69.77%) indicates the existence of moderate intersectional effects. We also found that SDoH factors such as slum location, mother’s employment, age of household head, and household’s garbage disposal system are associated with U5y health outcomes. The variables used in this analysis have low ability to distinguish between those with and without health outcomes. However, the existence of moderate intersectional effect estimates indicates that U5y in some social groups have worse health outcomes compared to others. Therefore, policymakers need to consider different social groups when designing intervention policies aimed to improve U5y health outcomes in Bangladesh slums.
Transforming medical education in Liberia through an international community of inquiry
Authors: Talbert-Slagle Kristina , Ajami Ibrahim , Currey Braden , Galvao Rachel , Hadush Jerusalem , Li Serene Silin , Flowers Javaughn T. , Ziah Moses , Amuh Desmond , Rabb Mikaela , Ilesanmi Olayinka Stephen , Allen Nikole , Martin Marie , Miller Mary , Yaman Attila , Nuthulaganti Tej , Plyler Chelsea , Kumeh Odell , Sieka Joseph , Ogbuagu Onyema , Marsh Regan , Rastegar Asghar , Sherman Lawrence , Adams Z’Sherman , Benson Angela , Dahn Bernice
Published: March 2023

A critical component of building capacity in Liberia’s physician workforce involves strengthening the country’s only medical school, A.M. Dogliotti School of Medicine. Beginning in 2015, senior health sector stakeholders in Liberia invited faculty and staff from U.S. academic institutions and non-governmental organizations to partner with them on improving undergraduate medical education in Liberia. Over the subsequent six years, the members of this partnership came together through an iterative, mutual-learning process and created what William Torbert et al describe as a “community of inquiry,” in which practitioners and researchers pair action and inquiry toward evidence-informed practice and organizational transformation. Incorporating faculty, practitioners, and students from Liberia and the U.S., the community of inquiry consistently focused on following the vision, goals, and priorities of leadership in Liberia, irrespective of funding source or institutional affiliation. The work of the community of inquiry has incorporated multiple mixed methods assessments, stakeholder discussions, strategic planning, and collaborative self-reflection, resulting in transformation of medical education in Liberia. We suggest that the community of inquiry approach reported here can serve as a model for others seeking to form sustainable global health partnerships focused on organizational transformation.
Luxeptinib interferes with LYN-mediated activation of SYK and modulates BCR signaling in lymphoma
Authors: Sonowal Himangshu , Rice William G. , Howell Stephen B.
Published: March 2023

Luxeptinib (LUX) is a novel oral kinase inhibitor that inhibits FLT3 and also interferes with signaling from the BCR and cell surface TLRs, as well as activation of the NLRP3 inflammasome. Ongoing clinical trials are testing its activity in patients with lymphoma and AML. This study sought to refine understanding of how LUX modulates the earliest steps downstream of the BCR following its activation by anti-IgM in lymphoma cells in comparison to ibrutinib (IB). LUX decreased anti-IgM-induced phosphorylation of BTK at Y551 and Y223 but its ability to reduce phosphorylation of kinases further upstream suggests that BTK is not the primary target. LUX was more effective than IB at reducing both steady state and anti-IgM-induced phosphorylation of LYN and SYK. LUX decreased phosphorylation of SYK (Y525/Y526) and BLNK (Y96) which are necessary regulators of BTK activation. Further upstream, LUX blunted the anti-IgM-induced phosphorylation of LYN (Y397) whose activation is required for phosphorylation of SYK and BLNK. These results indicate that LUX is targeting autophosphorylation of LYN or a step further upstream of LYN in the cascade of signal generated by BCR and that it does so more effectively than IB. The fact that LUX has activity at or upstream of LYN is important because LYN is an essential signaling intermediate in multiple cellular signaling processes that regulate growth, differentiation, apoptosis, immunoregulation, migration and EMT in normal and cancer cells.
Knockout of DDM1 in Physcomitrium patens disrupts DNA methylation with a minute effect on transposon regulation and development
Authors: Griess Ofir , Domb Katherine , Katz Aviva , Harris Keith D. , Heskiau Karina G. , Ohad Nir , Zemach Assaf
Published: March 2023

The Snf2 chromatin remodeler, DECREASE IN DNA METHYLATION 1 (DDM1) facilitates DNA methylation. In flowering plants, DDM1 mediates methylation in heterochromatin, which is targeted primarily by MET1 and CMT methylases and is necessary for silencing transposons and for proper development. DNA methylation mechanisms evolved throughout plant evolution, whereas the role of DDM1 in early terrestrial plants remains elusive. Here, we studied the function of DDM1 in the moss,Physcomitrium (Physcomitrella) patens, which has robust DNA methylation that suppresses transposons and is mediated by a MET1, a CMT, and a DNMT3 methylases. To elucidate the role of DDM1 inP.patens, we have generated a knockout mutant and found DNA methylation to be strongly disrupted at any of its sequence contexts. Symmetric CG and CHG sequences were affected stronger than asymmetric CHH sites. Furthermore, despite their separate targeting mechanisms, CG (MET) and CHG (CMT) methylation were similarly depleted by about 75%. CHH (DNMT3) methylation was overall reduced by about 25%, with an evident hyper-methylation activity within lowly-methylated euchromatic transposon sequences. Despite the strong hypomethylation effect, only a minute number of transposons were transcriptionally activated inPpddm1. Finally,Ppddm1was found to develop normally throughout the plant life cycle. These results demonstrate that DNA methylation is strongly dependent on DDM1 in a non-flowering plant; that DDM1 is required for plant-DNMT3 (CHH) methylases, though to a lower extent than for MET1 and CMT enzymes; and that distinct and separate methylation pathways (e.g. MET1-CG and CMT-CHG), can be equally regulated by the chromatin and that DDM1 plays a role in it. Finally, our data suggest that the biological significance of DDM1 in terms of transposon regulation and plant development, is species dependent.
Green synthesized silver nanoparticles from eucalyptus leaves can enhance shelf life of banana without penetrating in pulp
Authors: Nayab Durr-e- , Akhtar Shamim
Published: March 2023

Bananas are exposed to serious post-harvest problems resulting in agricultural and economic losses across the world. The severity of problem is linked with the process of rapid ripening and pathogens attack. Such problems have led to economic losses as well as a lower yield of nutritionally rich bananas. The global demand to increase the life span of bananas and their protection from pathogens-borne diseases urged the use of antimicrobial edible coatings of nanoparticles. The present experiment has explored the innovative development of green synthesized nanoparticles from Eucalyptus leaf extract (ELE) to increase the shelf life of bananas up to 32 days from the day of collection. Statistically significant results were recorded (P = 0.05) by applying five different concentrations of silver nanoparticles (AgNPs) in ranges of 0.01–0.05%. Various morphological and physiological parameters such as color, decay, firmness, weight loss, pulp to peel ratio, pH, titrable acidity (TA), phenolic contents, protein estimation, ethylene production, starch content and total soluble sugars were measured in Cavendish banana (Basrai). Bananas treated with 0.01% AgNPs showed maximum control on its ripeness over morphological and physiological changes. The increase in shelf life was in order 0.01%>0.02%>0.03%>0.04%>0.05%> control. Further, AgNPs reduced the process of ripening by controlling ethylene production. The result has also proved the safety of banana consumption by simple removal of banana peel as penetration of AgNPs from the peel to the pulp was not detected. It is recommended to use 0.01% AgNPs to enhance the shelf life of banana without effecting its nutritive value.
Students’ intelligence test results after six and sixteen months of irregular schooling due to the COVID-19 pandemic
Authors: Breit Moritz , Scherrer Vsevolod , Blickle Joshua , Preckel Franzis
Published: March 2023

The COVID-19 pandemic has affected schooling worldwide. In many places, schools closed for weeks or months, only part of the student body could be educated at any one time, or students were taught online. Previous research discloses the relevance of schooling for the development of cognitive abilities. We therefore compared the intelligence test performance of 424 German secondary school students in Grades 7 to 9 (42% female) tested after the first six months of the COVID-19 pandemic (i.e., 2020 sample) to the results of two highly comparable student samples tested in 2002 (n= 1506) and 2012 (n= 197). The results revealed substantially and significantly lower intelligence test scores in the 2020 sample than in both the 2002 and 2012 samples. We retested the 2020 sample after another full school year of COVID-19-affected schooling in 2021. We found mean-level changes of typical magnitude, with no signs of catching up to previous cohorts or further declines in cognitive performance. Perceived stress during the pandemic did not affect changes in intelligence test results between the two measurements.
Dietary diversity modification through school-based nutrition education among Bangladeshi adolescent girls: A cluster randomized controlled trial
Authors: Nyma Zannatun , Rahman Mahfuzur , Das Subhasish , Alam Md Ashraful , Haque Enamul , Ahmed Tahmeed
Published: March 2023

Objective

To measure the efficacy of school-based nutrition education on dietary diversity of the adolescent girls in Bangladesh.

Methods

A matched, pair-cluster randomized controlled trial was conducted from July 2019 to September 2020. Randomization was done to select intervention and control schools. There were 300 participants (150 in the intervention and 150 in the control arm) at baseline. We randomly selected our study participants (adolescent girls) from grades six, seven, and eight of each school. Our intervention components included parents’ meetings, eight nutrition education sessions, and the distribution of information, education, and communication materials. An hour-long nutrition education session was provided using audio-visual techniques in a class of intervention school once a week by trained staffs of icddr,b for two months. Data on dietary diversity, anthropometry, socio-economic and morbidity status, a complete menstrual history, and haemoglobin status of adolescent girls were collected at recruitment and after five months of intervention. We calculated the mean dietary diversity score of adolescent girls at baseline and at the endline. As the dietary diversity score was incomparable between the control and intervention arm at baseline, we performed the difference-in-difference analysis to assess the effect of the intervention.

Results

Mean age of the adolescent girls was 12.31 years and 12.49 years in the control and intervention arms respectively. Percentages of consumption of organ meat, vitamin A-rich fruits and vegetables, legumes, nuts, and seeds were higher in the intervention arm than in the control arm at the end-line. The mean dietary diversity score remained unchanged in the control arm at 5.55 (95% CI: 5.34–5.76) at baseline and 5.32 (95% CI: 5.11–5.54) at the endline. After the intervention, mean dietary diversity increased from 4.89 (95% CI: 4.67–5.10) at baseline to this mean was 5.66 (95% CI: 5.43–5.88) at the endline. Result from the difference-in-difference analysis revealed that the mean dietary diversity was likely to increase by 1 unit due to intervention.

Conclusion

The shorter duration of the intervention in our study could not show whether it could change the behavior of adolescent girls in increasing dietary diversity through school-based nutrition education, but it showed a pathway for increasing dietary diversity at school. We recommend including more clusters and other food environment elements in retesting to increase precision and acceptability.

Trial registration

This study was registered with ClinicalTrials.gov, trial registration no: NCT04116593. https://clinicaltrials.gov/ct2/show/NCT04116593.