bluuebunny/crossref_metadata_2025 huggingface dataset:
Usability of Self-Management for Amputee Rehabilitation using Technology (SMART): An online self-management program for users with lower limb loss
Authors: Esfandiari Elham , Miller William C. , King Sheena
Published: June 2022

Background:

Individuals with lower limb loss (LLL) need education to adapt to their amputation. Self-management programs provide education and supportive skills to manage health-related physical and psychological challenges. eHealth technologies, such as online platforms, are increasing access to educational resources. We designed an online self-management program for individuals with LLL called Self-Management for Amputee Rehabilitation using Technology (SMART); however, before evaluating its efficacy, we wanted to understand its appropriateness in the target population.

Objective:

To assess the usability of SMART among individuals with LLL.

Study Design:

The study used a concurrent and retrospective think-aloud process.

Methods:

Individuals with LLL, aged 18 years or older (n = 9), reviewed the modules during an online video conferencing session with an assessor. SMART included four stakeholder-informed modules with 18 total sections. Participants were asked to think aloud while completing 11 SMART tasks, such as entering SMART, goal setting, finding skin care, and reading the content of 10 sections, including limb care, diet, fatigue, and energy. The interviews were transcribed verbatim and analyzed using directed content analysis.

Results:

The median age was 58 (range: 30–69) years. Overall, SMART was perceived as straightforward, easy to navigate, and an accessible resource for education and skills. Difficulties were identified with navigation (e.g. skipping the “Foot care for diabetes” section), presentation (e.g. unclear audio), and language (e.g. pistoning and contracture).

Conclusions:

SMART was redesigned to address the usability issues. The next step is to explore the perceived usefulness of SMART for content and intention to use.
The impact of posture correction bands on the respiratory function of healthy adults in their twenties: The difference between men and women
Authors: Park Tae Sung , Kim Sang Hun , Jang Myung Hun , Kim Soo Yeon , Min Ji Hong , Shin Myung-Jun
Published: June 2022

Introduction:

Recently, interest in posture correction has increased in Korea owing to increased smartphone usage. However, there have been no studies to evaluate the impact of wearing a posture correction band with an abdominal band on breathing and respiratory function.

Materials and Methods:

A total of 32 healthy adults, consisting of 16 men (mean age: 23.19 ± 2.88) and 16 women (mean age: 19.69 ± 1.49) participated in this study. Pulmonary function tests were conducted before and after wearing posture correction bands.

Results:

In all the participants, forced vital capacity decreased significantly (P < .05) after wearing a posture correction band. The forced expiratory volume in 1 second and maximal inspiratory pressure decreased slightly (P > .05). The maximal expiratory pressure (MEP) and peak cough flow (PCF) increased slightly (P > .05). When respiratory functions were monitored separately in men and women after wearing a posture correction band, forced vital capacity and forced expiratory volume in 1 second were significantly reduced in men (P < .05). In women, MEP and PCF increased significantly (P < .05).

Conclusions:

In this study, we confirmed that the posture correction band had an effect on respiratory function. Lung capacity was statistically significantly reduced but was not clinically significant. In addition, in the case of women, it was confirmed that the abdominal band improved the MEP and PCF.
Large Isolated Nasoorbital Type of Frontoethmoidal Encephalomeningocele
Authors: Charoenvicha Chirakan , Khwanngern Krit , Sirimaharaj Wimon
Published: June 2022

Frontoethmoidal encephalomeningocele (FEEM) is a rare congenital craniofacial malformation with increased incidence in Southeast Asia, especially in Thailand. Because of its rarity, main treatment obstacles include the lack of surgical treatment techniques and long-term postoperative follow-up data. The authors present the case of a 9-month-old boy who was born with a large isolated nasoorbital type of FEEM, which had a pressure effect on his right eye, nose, and facial complex. Preoperative computed tomography of the facial bone was performed to evaluate the external bony defect. This study aims to present surgical correction of FEEM with Chula's technique and long-term 7-year postoperative follow-up including both clinical and imaging aspects.
Novel Complement C5 Small-interfering RNA Lipid Nanoparticle Prolongs Graft Survival in a Hypersensitized Rat Kidney Transplant Model
Authors: Ishigooka Hidetoshi , Katsumata Haruki , Saiga Kan , Tokita Daisuke , Motoi Sotaro , Matsui Chiyuki , Suzuki Yuta , Tomimatsu Ayaka , Nakatani Tomoya , Kuboi Yoshikazu , Yamakawa Takafumi , Ikeda Takashi , Ishii Rumi , Imai Toshio , Takagi Toshio , Tanabe Kazunari
Published: June 2022

Background.

Prophylaxis of antibody-mediated rejection (AMR) caused by donor-specific antibodies remains challenging. Given the critical roles of complement activity in antibody-mediated graft injury, we developed a lipid nanoparticle (LNP) formulation of small-interfering RNA against complement C5 (C5 siRNA-LNP) and investigated whether C5 siRNA-LNP could downregulate the complement activity and act as an effective treatment for AMR.

Methods.

Lewis recipient rats were sensitized by skin grafting from Brown Norway donor rats. Kidney transplantation was performed at 4 wk post–skin grafting.

C5 siRNA- or control siRNA-LNP was administered intravenously, and the weekly injections were continued until the study’s conclusion. Cyclosporin (CsA) and/or deoxyspergualin (DSG) were used as adjunctive immunosuppressants. Complement activity was evaluated using hemolysis assays. The deposition of C5b9 in the grafts was evaluated using immunohistochemical analysis on day 7 posttransplantation.

Results.

C5 siRNA-LNP completely suppressed C5 expression and complement activity (hemolytic activity ≤ 20%) 7 d postadministration. C5 siRNA-LNP in combination with CsA and DSG (median survival time: 56.0 d) prolonged graft survival compared with control siRNA-LNP in combination with CsA and DSG (median survival time: 21.0 d; P = 0.0012; log-rank test). Immunohistochemical analysis of the grafts revealed that downregulation of C5 expression was associated with a reduction in C5b9-positive area (P = 0.0141, Steel-Dwass test).

Conclusions.

C5 siRNA-LNP combined with immunosuppressants CsA and DSG downregulated C5 activity and significantly prolonged graft survival compared with control siRNA-LNP with CsA and DSG. Downregulation of C5 expression using C5 siRNA-LNP may be an effective therapeutic approach for AMR.
Updated Views on Neutrophil Responses in Ischemia–Reperfusion Injury
Authors: Shepherd Hailey M. , Gauthier Jason M. , Terada Yuriko , Li Wenjun , Krupnick Alexander S. , Gelman Andrew E. , Kreisel Daniel
Published: June 2022

Ischemia–reperfusion injury is an inevitable event during organ transplantation and represents a primary risk factor for the development of early graft dysfunction in lung, heart, liver, and kidney transplant recipients. Recent studies have implicated recipient neutrophils as key mediators of this process and also have found that early innate immune responses after transplantation can ultimately augment adaptive alloimmunity and affect late graft outcomes. Here, we discuss signaling pathways involved in neutrophil recruitment and activation after ischemia-mediated graft injury in solid organ transplantation with an emphasis on lung allografts, which have been the focus of recent studies. These findings suggest novel therapeutic interventions that target ischemia–reperfusion injury-mediated graft dysfunction in transplant recipients.
Belatacept Treatment of Recurrent Late-onset T Cell–mediated Rejection/Antibody-mediated Rejection With De Novo Donor-specific Antibodies in a Liver Transplant Patient
Authors: Klintmalm Göran B. , Trotter James F. , Demetris Anthony
Published: June 2022

Background.

T cell–mediated rejection that appears and persists late after transplantation is often associated with development of de novo donor-specific antibodies. Treatment of this condition often presents a conundrum because of the uncertainty regarding the trade-off between immunosuppression-related toxicities/complications and restoration of allograft function and structure.

Methods.

Herein, we report an illustrative case of a young 20-y-old otherwise healthy woman who underwent liver replacement for Alagille’s syndrome from an ABO-compatible, 6 antigen-mismatched crossmatch-negative 24-y-old man. Although triple baseline immunosuppression was used (tacrolimus, mycophenolate mofetil, and prednisone), she developed rejection 3 d after liver replacement. Despite verified continual immunosuppression compliance, 1.5 y after liver replacement she experienced 6 more rejection episodes over the following 18 mo and development of de novo donor-specific antibody.

Results.

Treatment with belatacept began 3.5 y after transplantation, normalizing her liver tests with no further rejections. A biopsy obtained 6 y after transplantation (postoperative day 2221) was normal, appearing without inflammation or residual fibrosis.

Conclusions.

Belatacept may be a useful treatment approach in this setting.
Establishment of a reverse genetics system for avian rotavirus A strain PO-13
Authors: Kanda Marika , Fukuda Saori , Hamada Nanami , Nishiyama Shoko , Masatani Tatsunori , Fujii Yuji , Izumi Fumiki , Okajima Misuzu , Taniguchi Koki , Sugiyama Makoto , Komoto Satoshi , Ito Naoto
Published: June 2022

Avian rotavirus A (RVA) is one of major enteric pathogens that cause diarrhoea in young avian individuals. Importantly, some of the avian RVA strains of G18P[17] genotype are naturally transmitted to and cause clinical diseases in mammalian species, indicating their potential risks to animal health. Although molecular information on the pathogenesis by avian RVA strains will be useful for estimating their risks, the absence of a reverse genetics (RG) system for these strains has hindered the elucidation of their pathogenic mechanisms. In this study, we aimed to establish an RG system for the avian G18P[17] prototype strain PO-13, which was isolated from a pigeon in Japan in 1983 and was experimentally shown to be pathogenic in suckling mice. Transfection with plasmids expressing 11 genomic RNA segments of the strain resulted in rescue of the infectious virus with an artificially introduced genetic marker on its genome, indicating that an RG system for the PO-13 strain was successfully established. The rescued recombinant strain rPO-13 had biological properties almost identical to those of its wild-type strain (wtPO-13). Notably, both rPO-13 and wtPO-13 induced diarrhoea in suckling mice with similar efficiencies. It was thus demonstrated that the RG system will be useful for elucidating the pathogenic mechanisms of the PO-13 strain at the molecular level. This is the first report of the establishment of an RG system for an avian RVA strain.
Notch2 signaling guides B cells away from germinal centers towards marginal zone B cell and plasma cell differentiation
Authors: Babushku T. , Lechner M. , Yates A. J. , Rane S. , Zimber-Strobl U. , Strobl L. J.
Published: June 2022

Notch2 signaling has a profound role in driving the development of Marginal Zone B (MZB) cells. We recently demonstrated that Follicular B (FoB) cells act as precursors for MZB cells in mice, but the mechanistic aspects of this differentiation pathway are still elusive. By studying Notch signaling in CBF:H2B-Venus Notch-reporter mice, we show that most B cells receive a Notch signal, which is highest in MZB cells. However, surprisingly, around one-third of MZB cells seem to lose their Notch signal with time. Conditional deletion or constitutive activation of Notch2 in mice upon T-cell-dependent (TD) immunization unraveled an interplay between antigen-induced activation and Notch2 signaling, in which FoB cells that turn off the Notch pathway enter germinal centers, whereas FoB cells with high Notch signals undergo MZB cell or plasmablast differentiation. Input of experimental data into a mathematical modeling framework reveals that MZB cells regularly emerge from antigen-activated FoB cells in a Notch2-dependent manner upon TD immunization.
Exploring Religious leaders’ experiences and challenges on Childbirth at Health Institutions. A qualitative study
Authors: Abebe Lakew , Birhanu Zewdie , Bergen Nicole , Bulcha Gebeyehu , Haji Kunuz , Kulkarni Manisha , Kurji Jaameeta , Abera Mulumebet , Mamo Abebe , Labonté Ronald , Morankar Sudhakar
Published: June 2022

Background

Childbirth at health institutions is critical to preventing major maternal and newborn deaths. In low and middle-income countries, many women still give childbirth without skilled assistance. Religious leaders may play a crucial role to promote childbirth at health institutions. So, this study aims to explore religious leaders’ experiences and challenges in childbirth preparedness and childbirth at health institutions.

Methods

After ethical approval was secured from Jimma University, Ethiopia, and the University of Ottawa, Health Sciences and Research Ethics Boards, Canada an exploratory study was conducted from Nov 2016 to February 2017.

Data were collected from 24 religious leaders. Atlas ti software 7.5.18 package was used to assist the analysis. Identified themes and categories were interpreted and discussed with related studies.

Results

Lower awareness level, family needs for traditional birth rituals at home, lack of access to roads and transportation, lack of medical supplies, poor quality of health care provision and lack of respect for laboring mothers were the challenges raised by study participants. There was a traditional way of childbirth preparedness but is not matched due to economic status and level of awareness. The majority are inclined to say that destiny of maternal health outcome is determined by God/Allah’s will though not contradicting childbirth at a health institution.

Conclusion

A comprehensive approach to include religious leaders to increase awareness and positive beliefs towards childbirth at health institutions should be considered. Health institution factors such as respect for laboring mothers, medical supplies, and equipment should be improved. Access to roads or transportation also needs to be communicated to responsible bodies and community leaders to improve transportation problems.
Hox11-expressing interstitial cells contribute to adult skeletal muscle at homeostasis
Authors: Flynn Corey G.K. , Guo Qingyuan , Van Ginkel Paul R. , Hrycaj Steven M. , McDermott Aubrey E. , Madruga Angelo , Wellik Deneen M.
Published: June 2022

Adult skeletal muscle possesses remarkable regenerative capacity. This is attributed to tissue-specific stem cells, satellite cells. Interstitial stromal cells also play critical roles in muscle, and we have previously reported that Hoxa11 and Hoxd11, expressed in the interstitial cells of muscles that attach to the zeugopod (radius and ulna), are critical for the proper patterning and development of these muscles during embryogenesis. Using a Hoxa11eGFP knock-in reporter, we show that expression continues in a subset of muscle interstitial cells through adult stages. Using Hoxa11-CreERT2 mediated lineage reporting induced at adult stages, we observe lineage initiation only in the interstitial cells of muscle, as expected. However, this Hoxa11-expressing interstitial cell lineage progressively contributes to muscle fibers at postnatal and adult stages. The contribution to these muscles at adult homeostasis significantly exceeds parallel Pax7-CreERT2 mediated lineage labeling performed in parallel. To confirm that interstitial cell nuclear contents are contributed to muscle fibers, we additionally used the nuclear specific lineage reporter, ROSA-LSL-H2BmCherry with Hoxa11-CreERT2 and observe that Hoxa11-expressing interstitial cells contribute their nuclei to myofibers. Hox lineage contribution is observed into all four muscle sub-types over months of lineage labeling. At no point after Hoxa11-mediated lineage induction do we observe lineage labeling into Pax7-expressing satellite cells. This adds to a small but growing body of evidence that supports a satellite cell-independent source of muscle tissue in vivo.

Summary Statement

Hoxa11 expression marks a novel population of muscle interstitial cells capable of extensive, satellite cell-independent contribution to skeletal muscle fibers during adult homeostasis.
Viral load and timing of infection define neutralization diversity to SARS-CoV-2 infection
Authors: Miyamoto Sho , Arashiro Takeshi , Ueno Akira , Kanno Takayuki , Saito Shinji , Katano Harutaka , Iida Shun , Ainai Akira , Ozono Seiya , Hemmi Takuya , Hirata Yuichiro , Moriyama Saya , Kotaki Ryutaro , Kinoshita Hitomi , Yamada Souichi , Shinkai Masaharu , Fukushi Shuetsu , Takahashi Yoshimasa , Suzuki Tadaki
Published: June 2022

Immunity to SARS-CoV-2 in COVID-19 cases has diversified due to complex combinations of exposure to vaccination and infection. Elucidating the drivers for upgrading neutralizing activity to SARS-CoV-2 in COVID-19 cases with pre-existing immunity will aid in understanding immunity to SARS-CoV-2 and improving COVID-19 booster vaccines with enhanced cross-protection against antigenically distinct variants. This study revealed that the magnitude and breadth of neutralization responses to SARS-CoV-2 infection in breakthrough infections are determined by upper respiratory viral load and vaccination-infection time interval, but not by the lineage of infecting viruses. Notably, the time interval, but not the viral load, may play a critical role in expanding the breadth of neutralization to SARS-CoV-2. This illustrates the importance of dosing interval optimization in addition to antigen design in the development of variant-proof booster vaccines.

One-Sentence Summary

Viral load and infection timing define the magnitude and breadth of SARS-CoV-2 neutralization after breakthrough infection.
PlantCADB: A comprehensive plant chromatin accessibility database
Authors: Ding Ke , Sun Shanwen , Long Chaoyue , Luo Yang , Zhai Jingwen , Zhai Yixiao , Wang Guohua
Published: June 2022

Chromatin accessibility landscapes are essential for detecting regulatory elements, illustrating the corresponding regulatory networks, and, ultimately, understanding the molecular bases underlying key biological processes. With the advancement of sequencing technologies, a large volume of chromatin accessibility data has been accumulated and integrated in humans and other mammals. These data have greatly advanced the study of disease pathogenesis, cancer survival prognosis, and tissue development. To advance the understanding of molecular mechanisms regulating plant key traits and biological processes, we developed a comprehensive plant chromatin accessibility database (PlantCADB, https://bioinfor.nefu.edu.cn/PlantCADB/) from 649 samples of 37 species. Among these samples, 159 are abiotic stress-related (including heat, cold, drought, salt, etc.), 232 are development-related and 376 are tissue-specific. Overall, 18,339,426 accessible chromatin regions (ACRs) were compiled. These ACRs were annotated with genomic information, associated genes, transcription factors footprint, motif, and SNPs. Additionally, PlantCADB provides various tools to visualize ACRs and corresponding annotations. It thus forms an integrated, annotated, and analyzed plant-related chromatin accessibility information which can aid to better understand genetic regulatory networks underlying development, important traits, stress adaptions, and evolution.
Colour pattern edge contrast statistics can predict detection speed and success at ecologically relevant viewing distances in triggerfish (Rhinecanthus aculeatus)
Authors: van den Berg Cedric P. , Endler John A. , Papinczak Daniel E. J. , Cheney Karen L.
Published: June 2022

Edge detection is important for object detection and recognition. However, we do not know whether edge statistics predict the detection of prey by non-human predators. Understanding the link between image statistics and animal behaviour is crucial and of increasing importance given the growing availability of image analyses and their application across non-human visual systems. Here, we investigated whether Boundary Strength Analysis (BSA), Local Edge Intensity Analysis (LEIA) and the Gabor Ratio (GabRat) could predict the speed and success with which triggerfish (Rhinecanthus aculeatus) detected patterned circular stimuli against a noisy visual background, in both chromatic and achromatic presentations. We found that individual pattern statistics could only explain up to 2% of the variation in detection time, whereas PCA regression analysis considering all edge statistics simultaneously explained up to 6% of the variation. This suggests that other factors explained more behavioural variation than individual edge statistics. Furthermore, different statistics significantly correlated with detection speed depending on treatment, viewing distance, and changes in fish response over time, while highlighting the importance of considering spatial acuity and relevant viewing distances in the study of visual signals. Our results demonstrate the need for broad and unbiased approaches for identifying task-specific predictive relationships between pattern statistics and animal behaviour using image statistics capturing different aspects of colour patterns. We require robust statistical approaches to investigate correlations between ecological effect and the ever-increasing dimensionality and size of datasets in the field of visual ecology, rather than pre-emptively narrowing down the choice of image statistics unless warranted by specific hypotheses.

Summary statement

Correlations between edge detecting colour pattern statistics and animal behaviour are complex. Specifically, correlations are unlikely to be explained by single image statistics and depend upon observer distance.
Variation in symbiont density is linked to changes in constitutive immunity in the facultatively symbiotic coral, Astrangia poculata
Authors: Changsut Isabella , Womack Haley R. , Shickle Alicia , Sharp Koty H. , Fuess Lauren E.
Published: June 2022

Scleractinian corals are essential ecosystem engineers, forming the basis of coral reef ecosystems. However, these organisms are in decline globally, in part due to rising disease prevalence. Most corals are dependent on symbiotic interactions with single-celled algae from the family Symbiodiniaceae to meet their nutritional needs, however suppression of host immunity may be essential to this relationship. To explore immunological consequences of algal symbioses in scleractinian corals, we investigated constitutive immune activity in the facultatively symbiotic coral, Astrangia poculata. We compared immune metrics (melanin synthesis, antioxidant production, and antibacterial activity) between coral colonies of varying symbiont density. Symbiont density was positively correlated to both antioxidant activity and melanin concentration. Our results suggest that the relationship between algal symbiosis and host immunity may be more complex than originally hypothesized and highlight the need for nuanced approaches when considering these relationships.
NADPH oxidase promotes glioblastoma radiation resistance in a PTEN-dependent manner
Authors: Ludwig Kirsten , Le Belle Janel E. , Muthukrishnan Sree Deepthi , Sperry Jantzen , Condro Michael , Vlashi Erina , Pajonk Frank , Kornblum Harley I.
Published: June 2022

Aims

The goal of this study was to determine whether NADPH oxidase (NOX)-produced reactive oxygen species enhances brain tumor growth of glioblastoma (GBM) under hypoxic conditions and during radiation treatment.

Results

Exogenous ROS promoted brain tumor growth in gliomasphere cultures that expressed functional PTEN, but not in tumors that were PTEN deficient. Hypoxia induced the production of endogenous cytoplasmic ROS and tumor cell growth via activation of NOX. NOX activation resulted in oxidation of PTEN and downstream Akt activation. Radiation also promoted ROS production via NOX which, in turn, resulted in cellular protection that could be abrogated by knockdown of the key NOX component, p22. Knockdown of p22 also inhibited tumor growth and enhanced the efficacy of radiation in PTEN-expressing GBM cells.

Innovation

While other studies have implicated NOX function in GBM models, these studies demonstrate NOX activation and function under physiological hypoxia and following radiation in GBM, two conditions that are seen in patients. NOX plays an important role in a PTEN-expressing GBM model system, but not in PTEN-non-functional systems and provide a potential, patient-specific therapeutic opportunity.

Conclusions

This study provides a strong basis for pursuing NOX inhibition in PTEN-expressing GBM cells as a possible adjunct to radiation therapy.
A unitary model of auditory frequency change perception
Authors: Siedenburg Kai , Graves Jackson , Pressnitzer Daniel
Published: June 2022

Changes in the frequency content of sounds over time are arguably the most basic form of information about the behavior of sound-emitting objects. In perceptual studies, such changes have mostly been investigated separately, as aspects of either pitch or timbre. Here, we propose a unitary account of “up” and “down” subjective judgments of frequency change, based on a model combining auditory correlates of acoustic cues in a sound-specific and listener-specific manner. To do so, we introduce a generalized version of so-called Shepard tones, allowing symmetric manipulations of spectral information on a fine scale, usually associated to pitch (spectral fine structure, SFS), and on a coarse scale, usually associated timbre (spectral envelope, SE). In a series of behavioral experiments, listeners reported “up” or “down” shifts across pairs of generalized Shepard tones that differed in SFS, in SE, or in both. We observed the classic properties of Shepard tones for either SFS or SE shifts: subjective judgements followed the smallest log-frequency change direction, with cases of ambiguity and circularity. Interestingly, when both SFS and SE changes were applied concurrently (synergistically or antagonistically), we observed a trade-off between cues. Listeners were encouraged to report when they perceived “both” directions of change concurrently, but this rarely happened, suggesting a unitary percept. A computational model could accurately fit the behavioral data by combining different cues reflecting frequency changes after auditory filtering. The model revealed that cue weighting depended on the nature of the sound. When presented with harmonic sounds, listeners put more weight on SFS-related cues, whereas inharmonic sounds led to more weight on SE-related cues. Moreover, these stimulus-based factors were modulated by inter-individual differences, revealing variability across listeners in the detailed recipe for “up” and “down” judgments. We argue that frequency changes are tracked perceptually via the adaptive combination of a diverse set of cues, in a manner that is in fact similar to the derivation of other basic auditory dimensions such as spatial location.
High-flow nasal cannula for acute exacerbation of chronic obstructive pulmonary disease: a Cost-utility analysis
Authors: Buendía Jefferson Antonio , Guerrero Patiño Diana
Published: June 2022

Background

High-flow nasal cannula (HFNC) is an alternative for delivering respiratory support to adults with acute exacerbations of chronic obstructive pulmonary disease. Despite increased popularity for respiratory support, there is still uncertainty about if their l costs of justify the clinical benefits provided. This study aims to evaluate the cost-utility of HFNC in acute exacerbations of chronic obstructive pulmonary disease in Colombia

Methods

Using a decision tree model, we estimated the cost and quality-adjusted life-years (QALYs) associated with HFNC and conventional oxygen therapy (COT) in adults who presented to the emergency department with acute exacerbations of chronic obstructive pulmonary disease. All parameters for the model were derived from published research with local data. All analyses were done from a societal perspective.

Results

We estimate a gain of 0,49 and 0,48 QALYs per patient-year on HFNC and COT respectively, and a difference of US$314 in total discounted cost per person-year on HFNC respecting COT. Because HFNC was associated with lower costs compared to conventional therapy, the incremental cost effectiveness ratio was not calculated.

Conclusions

HFNC achieving better outcomes at a lower cost in patients with acute exacerbations of chronic obstructive pulmonary disease in Colombia. Evidence should continue to be generated with real-life effectiveness data and economic evaluations in other countries to confirm our findings.
The prevalence and management strategies of gestational urinary tract infections (UTI) in Kisumu County, Kenya
Authors: Toko Eunice Namuyenga , Samarasinghe Shivanthi , Furaha Esther , Kapasi Tariq , Ochieng’ Bertha , Ouma Collins
Published: June 2022

Background

Urinary tract infections (UTI) contribute to substantive proportions of adverse pregnancy outcomes. Current national statistics in Kenya show high maternal mortality (488/100,000) and neonatal mortality (24/1,000) rates. Kenya continues to report increasing prevalence and incidence rates of UTI associated with maternal and neonatal deaths. Kisumu County in western Kenya has a high maternal mortality rate of 495/100,000 with uncaptured maternal morbidity relative to the national average. However, information on the epidemiology of gestational UTI in the County, is limited. Semi-urban Chulaimbo and Nyahera Sub-County hospitals were used as model facilities to establish the burden of UTI during pregnancy and the specific clinical diagnosis and therapeutic management strategies.

Methods

Socio-demographic, laboratory and clinical history data was extracted from 416 pregnant women’s maternal child health data sets from health records between February 2019 to February 2020 using pre-designed data collection forms. Descriptive analysis was used to summarize the study population’s demographic characteristics. Chi-square test was used to establish proportionality. Qualitative data were thematically summarized. For all analyses, P≤0.05 was considered statistically significant.

Results

The study population had a mean of two (2) (±1.14) ante-natal (ANC) visits; a mean mothers age of 23.92 (± 6) years old; a mean parity of 2 (±2) and a mean haemoglobin level of 10.73(±1.8). About 56% (233/416) of the mothers attended the first ANC visit at varied gestational age. Only 1.4% (6/416) had a clinical history capturing UTI infection out of the total prevalence of 57.9% (241/416) diagnosed UTI positive by routine ANC profile deep stick urinalysis test. These clinical history data sets 1.4% (6/416) revealed a broad-spectrum therapeutic management of gestational bacterial infections using first line antibiotics.

Conclusions

Most UTI positive cases go without specific clinical diagnosis and management, posing a high risk of antibiotic drug resistance and development of specific bacterial allied gestational complications.
An exploration of methods to enable equitable access to non-invasive prenatal screening
Authors: Ehrich Mathias , Sagaser Katelynn G. , Ellison Christopher K. , Wu Allison Chia-Yi , Hutchison Don C. , Porreco Richard P. , Bellesheim Deborah , Patil Avinash S. , Shulman Lee P. , van den Boom Dirk
Published: June 2022

Objective

To explore capillary blood collection as a potential method to enable more equitable access to non-invasive prenatal screening (NIPS) for aneuploidy.

Methods

All participants contributed venous and capillary blood samples in this comparative study. Samples were analyzed using standard NIPS methods. Venous samples were used as the basis. Multiple parameters were compared including specimen collection, cfDNA characteristics, and NIPS outcome.

Results

Venous and capillary sample pairs were successfully collected for comparative analysis from 202 participants. Cell free DNA (cfDNA) size profiles from venous vs capillary blood were not different (p >0.05). Evaluation of fetoplacental cfDNA contribution in plasma revealed no statistically significant difference in venous vs capillary samples. Elevated Z-scores for trisomy 21 (n=13), trisomy 18 (n=2), or trisomy 13 (n=1) were concordant between venous and capillary samples in all 16 pairs.

Conclusion

We have demonstrated that sufficient capillary blood volumes can be obtained for NIPS. Furthermore, capillary and venous cfDNA samples have comparable characteristics. As NIPS results from capillary blood collections are equivalent to NIPS results obtained from venous blood, capillary blood collections are a potential candidate for a distributable NIPS system which promotes equitable access to NIPS for all pregnant patients.
Evolutionary dynamics in non-Markovian models of microbial populations
Authors: Jafarpour Farshid , Levien Ethan , Amir Ariel
Published: June 2022

In the past decade, great strides have been made to quantify the dynamics of single-cell growth and division in microbes. In order to make sense of the evolutionary history of these organisms, we must understand how features of single-cell growth and division influence evolutionary dynamics. This requires us to connect processes on the single-cell scale to population dynamics. Here, we consider a model of microbial growth in finite populations which explicitly incorporates the single-cell dynamics. We study the behavior of a mutant population in such a model and ask: can the evolutionary dynamics be coarse-grained so that the forces of natural selection and genetic drift can be expressed in terms of the long-term fitness? We show that it is in fact not possible, as there is no way to define a single fitness parameter (or reproductive rate) that defines the fate of an organism even in a constant environment. This is due to fluctuations in the population averaged division rate. As a result, various details of the single-cell dynamics affect the fate of a new mutant independently from how they affect the long-term growth rate of the mutant population. In particular, we show that in the case of neutral mutations, variability in generation times increases the rate of genetic drift, and in the case of beneficial mutations, variability decreases its fixation probability. Furthermore, we explain the source of the persistent division rate fluctuations and provide analytic solutions for the fixation probability as a multi-species generalization of the Euler-Lotka equation.
Rapid eco-phenotypic feedbacks and the temperature response of biomass dynamics
Authors: Gibert Jean P. , Wieczynski Daniel J. , Han Ze-Yi , Yammine Andrea
Published: June 2022

As biomass dynamics capture information on population dynamics and ecosystem-level processes (e.g., changes in production over time), understanding how rising temperatures associated with global climate change influence biomass dynamics is a pressing issue in ecology. The total biomass of a species depends on its density and its average mass. Disentangling how biomass dynamics may respond to increasingly warm and variable temperatures may thus ultimately depend on understanding how temperature influences both density and mass dynamics. Here, we address this issue by keeping track of experimental microbial populations growing to carrying capacity for 15 days at two different temperatures in the presence and absence of temperature variability. We show that temperature influences biomass through its effects on density and mass dynamics, which have opposite effects on biomass and can offset each other. We also show that temperature variability influences biomass, but that effect is independent of any effects on density or mass dynamics. Last, we show that reciprocal effects of density and mass shift significantly across temperature regimes, suggesting that rapid and environment-dependent eco-phenotypic dynamics underlie biomass responses. Overall, our results connect temperature effects on population and phenotypic dynamics to explain how biomass responds to temperature regimes, thus shedding light on processes at play in cosmopolitan and massively abundant microbes as the world experiences increasingly hot and variable temperatures.
Sexual orientation disparities in depression and substance use among adults: Results from the Brazilian National Health Survey, 2019
Authors: Gomes Nayara L. , Lopes Claudia S.
Published: June 2022

Purpose

To compare the prevalence of depression and substance use/abuse according to sexual orientation and sex among Brazilian adults.

Methods

Data were obtained from a national health survey (PNS 2019). This study included participants aged 18 and over (N=85,859). Prevalence ratios were estimated using Poisson models stratified by sex, for the association between sexual orientation, depression, daily tobacco use, alcohol abuse and both substance use/abuse.

Results

After controlling for covariates, gay men showed a higher prevalence of depression (APR=1.92, 95% CI 1.32; 2.80), daily tobacco use (APR=1.93, 95% CI 1.45; 2.56) and multiple substances use/abuse (APR=1.73, CI95% 1.14;2.62) than heterosexuals. Bisexual men showed higher prevalence of depression (APR=2.91, 95% CI 1.54; 5.53). Estimated prevalence ratios were even higher among women. Lesbians showed higher prevalence of binge drinking (APR=2.52, 95% CI 1.94; 3.27), heavy drinking (APR=3.36, 95% CI 2.39; 4.72), daily tobacco use (APR=2.66, 95% CI 1.74; 4.07) and multiple substances use/abuse (APR=4.35, 95% CI 2.35;8.07) than among heterosexuals. Among bisexual women, results were significant for all analyzed outcomes: depression (APR=2.32, 95% CI 1.72; 3.13), binge drinking (APR=2.52, 95% CI 1.94; 3.27), heavy drinking (APR=2.53, 95% CI 1.68; 3.81), daily tobacco use (APR=1.82, 95% CI 1.12;2.96) and multiple substances use/abuse (APR=3.23, 95% CI 1.72;6.05).

Conclusions

Our results indicate that sexual minorities are more vulnerable to mental illness and substance use/abuse. This finding draws attention to the need for specific public policies aimed at this population and for a greater recognition and better management of these disorders by health professionals.
Household Socio-demographic Characteristics and Progress towards Attainment of Universal Health Coverage in Kilimanjaro, Tanzania
Authors: Kimario Kanti Ambrose , Muhanga Mikidadi Idd , Kayunze Kim Abel
Published: June 2022

Universal Health Coverage (UHC) attainment has been associated with households’ socio-demographic characteristics. Empirical findings have hardly dwelt on assessing the association between household socio-demographic characteristics and UHC attainment. This article assessed the association between socio-demographic features and attainment of UHC in Kilimanjaro Region, Tanzania. Specifically, the article: (i) analysed the perceptions on households’ socio-demographic characteristics in relation to UHC factors; (ii) determined the association between socio-demographic characteristics and UHC attainment; and (iii) estimated the level of UHC service coverage in the study area. The study employed a cross-sectional research design in which 384 households were selected through a multi-stage sampling approach and interviewed using a questionnaire. The Kruskal Wallis H Test and Mann Whitney U test were used as tests for association of socio-demographic variables and UHC factors. Geometric mean computation was used to estimate the level of UHC attainment. Results indicate; the level of UHC service coverage score of 69.9%, which is fairly good in relation to the WHO recommendation of 80%. Occupation (p = 0.012), general household health condition (GHHC) (p=0.039), health insurance membership (HIM) (p=0.039), and presence of non-communicable disease (p=0.032) were significantly associated with health services delivery quality. GHHC (p=0.041) was significantly associated with service accessibility. Income (p=0.000), occupation (p=0.000), education (p=0.004), health check-up frequency (p=0.001), and HIM (p=0.000) were significantly associated with health services affordability. Health services accessibility was not of great concern to most of the households. Some households could easily afford the cost of health services and others could not. Service providers, LGAs and MoH should promote affordability and accessibility of health services by the population regardless of their socio-demographic characteristics. Promotion of a single universal health insurance fund is essential for an improved progress to UHC attainment.
Estimating RSV seasonality from pandemic disruptions: a modelling study
Authors: Krauer Fabienne , Fjelde Tor Erlend , Koltai Mihaly , Hodgson David , Treskova-Schwarzbach Marina , Harvey Christine , Jit Mark , Wichmann Ole , Harder Thomas , Flasche Stefan
Published: June 2022

Background

Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections and bronchiolitis in young children. The seasonal pattern of RSV is shaped by short-lived immunity, seasonally varying contact rates and pathogen viability. The magnitude of each of these parameters is not fully clear. The disruption of the regular seasonality of RSV during the COVID pandemic in 2020 due to control measures, and the ensuing delayed surge in RSV cases provides an opportunity to disentangle these factors and to understand the implication for vaccination strategies. A better understanding of the drivers of RSV seasonality is key for developing future vaccination strategies.

Methods

We developed a mathematical model of RSV transmission, which simulates the sequential re-infection (SEIRRS4) and uses a flexible Von Mises function to model the seasonal forcing. Using MCMC we fit the model to laboratory confirmed RSV data from 2010-2022 from NSW while accounting for the reduced contact rates during the pandemic with Google mobility data. We estimated the baseline transmission rate, its amplitude and shape during RSV season as well as the duration of immunity. The resulting parameter estimates were compared to a fit to pre-pandemic data only, and to a fit with a cosine forcing function. We then simulated the expected shifts in peak timing and amplitude under two vaccination strategies: continuous and seasonal vaccination.

Results

We estimate that RSV dynamics in NSW can be best explained by a high effective baseline transmission rate (2.94/d, 95% CrI 2.72-3.19) and a narrow peak with a maximum 13% increase compared to the baseline transmission rate. We also estimate the duration of post infection temporary but sterilizing immunity to be 412 days (95% CrI 391-434). A cosine forcing resulted in a similar fit and posterior estimates. Excluding the data from the pandemic period in the fit increased parameter correlation and yielded less informative posterior distributions. The continuous vaccination strategy led to more extreme seasonal incidence with a delay in the peak timing and a higher amplitude whereas seasonal vaccination flattened the incidence curves.

Conclusion

Quantifying the parameters that govern RSV seasonality is key in determining potential indirect effects from immunization strategies as those are being rolled out in the next few years.
Planar cell polarity: intracellular asymmetry and supracellular gradients of Dachsous
Authors: Chorro Adrià , Verma Bhavna , Homfeldt Maylin , Ibáñez Beatríz , Lawrence Peter A. , Casal José
Published: June 2022

The slope of a supracellular molecular gradient has long been thought to orient and coordinate planar cell polarity (PCP). Here we demonstrate and measure that gradient. Dachsous (Ds) is a conserved and elemental molecule of PCP; Ds forms intercellular bridges with another cadherin molecule, Fat (Ft), an interaction modulated by the Golgi protein Four- jointed (Fj). Using genetic mosaics and tagged Ds we measure Ds in vivo in membranes of individual cells over a whole metamere of the Drosophila abdomen. We find: 1. A supracellular gradient that rises from head to tail in the anterior compartment (A) and then falls in the posterior compartment (P). 2. There is more Ds in the front than the rear membranes of all cells in the A compartment, except that compartment’s most anterior and most posterior cells. There is more Ds in the rear than in the front membranes of all cells of the P compartment 3. The loss of Fj removes intracellular asymmetry anteriorly in the segment and reduces it elsewhere. Additional experiments show that Fj makes PCP more robust. Using Dachs (D) as a molecular indicator of polarity, we confirm that opposing gradients of PCP meet slightly out of register with compartment boundaries.
The effects of nitrogen deposition, grazing and land use on Danish acidic grasslands
Authors: Heltborg Winnie , Wendtland Danielsen Søren Ranum , Haugaard-Christensen Marianne , Frølund Damgaard Christian
Published: June 2022

It has been hypothesized that a strong interplay of land-use history may explain the weakening of the response of species richness to increased levels of nitrogen deposition in acid grasslands. In this study, we use an interpretation and grouping of crop codes from the farmers Field and Fertilizer Plan as an indicator for land use to test this hypothesis. We find that land-use, significantly, affects several indicators of the conservation status of Danish acid grasslands. The study clearly concludes that present and historical management and land-use is important for understanding the differences and changes in the conservation status of acid grassland.
Designed high-redox potential laccases exhibit high functional diversity
Authors: Barber-Zucker Shiran , Mateljak Ivan , Goldsmith Moshe , Kupervaser Meital , Alcalde Miguel , Fleishman Sarel J.
Published: June 2022

White-rot fungi secrete an impressive repertoire of high-redox potential laccases (HRPLs) and peroxidases for efficient oxidation and utilization of lignin. Laccases are attractive enzymes for green-chemistry applications due to their broad substrate range and low environmental impact. Since expression of functional recombinant HRPLs is challenging, however, iterative directed evolution protocols have been applied to improve their expression, activity and stability. We implement a rational, stabilize-and-diversify strategy to two HRPLs that we could not functionally express: first, we use the PROSS stability-design algorithm to allow functional expression in yeast. Second, we use the stabilized enzymes as starting points for FuncLib active-site design to improve their activity and substrate diversity. Four of the FuncLib designed HRPLs and their PROSS progenitor exhibit substantial diversity in reactivity profiles against high-redox potential substrates, including lignin monomers. Combinations of 3-4 subtle mutations that change the polarity, solvation and sterics of the substrate-oxidation site result in orders of magnitude changes in reactivity profiles. These stable and versatile HRPLs are a step towards the generation of an effective lignin-degrading consortium of enzymes that can be secreted from yeast. More broadly, the stabilize-and-diversify strategy can be applied to other challenging enzyme families to study and expand the utility of natural enzymes.