bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteosarcoma tumors maintain intra-tumoral transcriptional heterogeneity during bone and lung colonization
Authors: Rajan Sanjana , Franz Emily M. , McAloney Camille A. , Vetter Tatyana A. , Cam Maren , Gross Amy C. , Taslim Cenny , Wang Meng , Cannon Matthew V. , Oles Alexander , Roberts Ryan D.
Published: April 2023

Background

Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little of the mechanisms that govern heterogeneity of tumor cells nor of the role heterogeneity plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms—it exhibits widespread inter- and intra-tumoral heterogeneity, predictable patterns of metastasis, and a lack of clear targetable driver mutations. Understanding the processes that facilitate adaptation to primary and metastatic microenvironments could inform the development of therapeutic targeting strategies.

Results

We investigated single-cell RNA-sequencing profiles of 47,977 cells obtained from cell line and patient-derived xenograft models as cells adapted to growth within primary bone and metastatic lung environments. Tumor cells maintained phenotypic heterogeneity as they responded to the selective pressures imposed during bone and lung colonization. Heterogenous subsets of cells defined by distinct transcriptional profiles were maintained within bone- and lung-colonizing tumors, despite high-level selection. One prominent heterogenous feature involving glucose metabolism was clearly validated using immunofluorescence staining. Finally, using concurrent lineage tracing and single-cell transcriptomics, we found that lung colonization enriches for multiple clones with distinct transcriptional profiles that are preserved across cellular generations.

Conclusions

Response to environmental stressors occurs through complex and dynamic phenotypic adaptations. Heterogeneity is maintained, even in conditions that enforce clonal selection. These findings likely reflect the influences of developmental processes promoting diversification of tumor cell subpopulations, which are retained, even in the face of selective pressures.
CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure
Authors: Li Tushuai , Gu Yue , Xu Baocai , Kuca Kamil , Zhang Jie , Wu Wenda
Published: April 2023

CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed the viability, proliferation, and migration of RCC cells and inhibited tumorigenesis in xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins of circZBTB44. HNRNPC facilitated the translocation of circZBTB44 from nuclei to cytoplasm via m6A modification, facilitating the interaction of IGF2BP3 and circZBTB44 in the cytoplasm of RCC cells. Furthermore, circZBTB44 upregulated Hexokinase 3 (HK3) expression by binding to IGF2BP3 in RCC cells. HK3 exerted oncogenic effects on RCC cell malignant behaviors and tumor growth. In the co-culture of RCC cells with macrophages, circZBTB44 promoted M2 polarization of macrophages by up-regulating HK3. In summary, HNRNPC mediated circZBTB44 interaction with IGF2BP3 to up-regulate HK3, promoting the proliferation and migration of RCC cells in vitro and tumorigenesis in vivo. The results of the study shed new light on the targeted therapy of RCC.
Short and medium-term effects of the COVID-19 lockdowns on child and parent accelerometer-measured physical activity and sedentary time: a natural experiment
Authors: Jago Russell , Salway Ruth , House Danielle , Walker Robert , Emm-Collison Lydia , Sansum Kate , Breheny Katie , Reid Tom , Churchward Sarah , Williams Joanna G. , Foster Charlie , Hollingworth William , de Vocht Frank
Published: April 2023

Background

The COVID-19 pandemic has resulted in marked impacts on children’s physical activity, with large reductions in moderate-to-vigorous physical activity (MVPA) reported during lockdowns. Previous evidence showed children’s activity levels were lower and sedentary time higher immediately post-COVID lockdown, while there was little change in parental physical activity. We need to know if these patterns persist.

Methods

Active-6 is a natural experiment using repeated cross-sectional data conducted in two waves. Accelerometer data were collected on 393 children aged 10–11 and their parents from 23 schools in Wave 1 (June 2021-December 2021), and 436 children and parents from 27 schools in Wave 2 (January 2022-July 2022). These were compared to a pre-COVID-19 comparator group (March 2017-May 2018) of 1,296 children and parents in the same schools. Mean minutes of accelerometer-measured MVPA and sedentary time were derived for week- and weekend-days and compared across waves via linear multilevel models. We also analysed the date of data collection as a time series, to explore temporal patterns via generalised additive mixed models.

Results

There was no difference in children’s mean MVPA in Wave 2 (weekdays: -2.3 min; 95% CI: -5.9, 1.3 and weekends: 0.6 min; 95% CI: -3.5, 4.6) when compared to the pre-COVID-19 data. Sedentary time remained higher than pre-pandemic by 13.2 min (95% CI:5.3, 21.1) on weekdays. Differences compared to pre-COVID-19 changed over time, with children’s MVPA decreasing over winter, coinciding with COVID-19 outbreaks, and only returning to pre-pandemic levels towards May/June 2022. Parents’ sedentary time and weekday MVPA was similar to pre-COVID-19 levels, with MVPA higher than pre-pandemic by 7.7 min (95% CI: 1.4, 14.0) on weekends.

Conclusion

After an initial drop, children’s MVPA returned to pre-pandemic levels by July 2022, while sedentary time remained higher. Parents’ MVPA remained higher, especially at weekends. The recovery in physical activity is precarious and potentially susceptible to future COVID-19 outbreaks or changes in provision, and so robust measures to protect against future disruptions are needed. Furthermore, many children are still inactive, with only 41% meeting UK physical activity guidelines, and so there is still a need to increase children’s physical activity.
Gynecological morbidity and treatment-seeking among older adult (aged 45–59) women in India
Authors: Pradhan Manas Ranjan , Mondal Sourav , Mudi Prasanna Kumar
Published: April 2023

Background

Women’s gynecological health needs are not limited to the reproductive years of their life. Women are at risk of hormonal changes, gynecological malignancies, and various genitourinary conditions as they move toward menopause and beyond. Concerns about older women’s sexual and reproductive health and rights (SRHR) continue to be taboo in many countries, of little interest to researchers and professionals in the field of healthcare, and a “blind spot” in discussions about policy as a whole. Despite the widespread agreement, the life course approach to addressing SRHR concerns has received minimal attention. The study estimates the prevalence, assesses the correlates, and treatment-seeking of gynecological morbidity (GM) among older adult women aged 45–59 years (N = 18,547) in India.

Method

The analysis was based on the nationally representative Longitudinal Ageing Study (2016–2017) data that adopted a multistage stratified area probability cluster sampling to select respondents. The outcome variables used in this analysis were ‘had any GM’ and ‘sought treatment for any GM.’ Women with any morbidity such as per vaginal bleeding, foul-smelling vaginal discharge, uterus prolapses, mood swings/irritability, fibroid/cyst, and dry vagina causing painful intercourse were considered to have any GM. Of the respondents with GM, who sought a doctor’s consultation or treatment were considered ‘sought treatment for any GM.’ Binary logistic regression was conducted to examine the adjusted effect of socioeconomic and demographic predictors of GM and treatment-seeking. Stata (V 16) was used for statistical analyses with a 5% significance level.

Results

Fifteen percent of the women had any GM, and only 41% of them sought treatment. Age, marital status, education, number of pregnancies, hysterectomy, involvement in household decision-making, social group, religion, wealth status, and region were significantly associated with GM. The odds of treatment-seeking were higher among women with 10+ years of schooling (OR 1.66, CI 1.23, 2.23), with hysterectomy (OR 7.36, CI 5.92, 9.14), with five-plus pregnancies (OR 1.25, CI 0.96, 1.64), and those from the richest (OR 1.91, CI 1.40, 2.60) households than their respective counterparts.

Conclusion

Many older adult women experience GM, and treatment-seeking is inadequate. The GM prevalence and treatment-seeking vary considerably by socioeconomic and demographic characteristics. Results suggest community-level awareness generation and the inclusion of this otherwise ignored group in programs targeting better health and wellbeing of women.
Comparison of wrist actimetry variables of paretic upper limb use in post stroke patients for ecological monitoring
Authors: Dusfour Gilles , Mottet Denis , Muthalib Makii , Laffont Isabelle , Bakhti Karima
Published: April 2023

Background

To date, many wrist actimetric variables dedicated to measuring the upper limbs (UL) in post-stroke patients have been developed but very few comparisons have been made between them. The objective of this study was to compare different actimetric variables of the ULs between a stroke and healthy population.

Methods

Accelerometers were worn continuously for a period of 7 days on both wrists of 19 post-stroke hemiparetic patients as well as 11 healthy subjects. Various wrist actimetry variables were calculated, including the Jerk ratio 50 (JR50, cumulative probability that the Jerk Ratio is between 1 and 2), absolute (FuncUse30) and relative (FuncUseRatio30) amounts of functional use of movements of the ULs with angular amplitude greater than 30°, and absolute (UH) and relative (UseHoursRatio) use hours.

Results

FuncUse30, FuncUseRatio30, UH, UseHoursRatio and JR50 of the paretic UL of stroke patients were significantly lower than in the non-dominant UL of healthy subjects. Comparing the ratio variables in stroke patients, FuncUseRatio30 was significantly lower than UseHoursRatio and JR50, suggesting a more clinically sensitive variable to monitor. In an exploratory analysis, FuncUseRatio tends to decrease with angular range of motion for stroke patients while it remains stable and close to 1 for healthy subjects. UseHoursRatio, FuncUseRatio30 and JR50 show linear correlation with Fugl-Meyer score (FM), with r2equal to 0.53, 0.35 and 0.21, respectively.

Conclusion

This study determined that the FuncUseRatio30 variable provides the most sensitive clinical biomarker of paretic UL use in post-stroke patients, and that FuncUseHours—angular range of motion relationship allows the identification of the UL behaviour of each patient. This ecological information on the level of functional use of the paretic UL can be used to improve follow-up and develop patient-specific therapy.
Can elderly individuals perform partial weight bearing on their lower limbs? A prospective cohort study using ambulatory real-time biofeedback
Authors: Merkle Tobias Peter , Hofmann Nina , Knop Christian , Da Silva Tomas
Published: April 2023

Background

Partial weight bearing in an orthosis and with forearm crutches is a widespread and well-accepted therapeutic principle after an injury of the lower extremity during early rehabilitation. Complying may be challenging to do under these circumstances, especially for elderly people. This study compares the spatiotemporal parameters and peak loads performed by a group of older participants before and after activating real-time biofeedback (BF) to determine whether they benefit from a biofeedback.

Methods

Twenty-four healthy subjects between 61 and 80 years learned how to walk using forearm crutches in a lower leg orthosis while performing a weight of 20 kg using a bathroom scale with the aim of loading in a zone between 15 and 30 kg. After that, they completed a course that was on level ground (50 m) and another course on stairs (11 steps). They did a walk without BF first, and then with BF. Each step was given a maximum load, which was determined and statistically checked. In addition, spatiotemporal parameters were collected.

Results

The classical teaching method with a bathroom scale was ineffective. Only 32.3% of the loads could be adequately carried by a person on level ground in the 15–30 kg target zone. On the stairs, it was 48.2% and 34.3%, respectively. Thus, on level ground, 52.7% of loads exceeded 30 kg. Downstairs it was 46.4%, and upstairs it was 41.6%. Subjects clearly benefit from activated biofeedback. Biofeedback significantly reduced missteps > 30 kg in every course. The loads decreased significantly to 25.0% on level ground, to 23.0% upstairs, and to 24.4% downstairs. At the same time, speed and stride length decreased per course while total time increased.

Conclusion

Partial weight bearing is more complex and difficult for the elderly. These study results may help better understand 3-point gait in older adults in an outpatient setting. When partial weight bearing is recommended, special follow-up attention must be given for this group. Age-based therapy strategies can be developed and monitored with the assistance of ambulatory biofeedback devices.

Trial registrationRetrospectively registered,https://www.drks.de/DRKS00031136.
Mental health related stigma, service provision and utilization in Northern India: situational analysis
Authors: Kaur Amanpreet , Kallakuri Sudha , Mukherjee Ankita , Wahid Syed Shabab , Kohrt Brandon A. , Thornicroft Graham , Maulik Pallab K.
Published: April 2023

Stigma, discrimination, poor help seeking, dearth of mental health professionals, inadequate services and facilities all adversely impact the mental health treatment gap. Service utilization by the community is influenced by cultural beliefs and literacy levels. We conducted a situational analysis in light of the little information available on mental health related stigma, service provision and utilization in Haryana, a state in Northern India. This involved: (a) qualitative key informant interviews; (b) health facility records review; and (c) policy document review to understand the local context of Faridabad district in Northern India. Ethical approvals for the study were taken before the study commenced. Phone call in-depth interviews were carried out with a purposive sample of 13 participants (Mean = 38.07 years) during the COVID-19 pandemic, which included 4 community health workers, 4 people with mental illness, 5 service providers (primary health care doctors and mental health specialists). Data for health facility review was collected from local primary health and specialist facilities while key policy documents were critically analysed for service provision and stigma alleviation activities. Thematic analysis was used to analyse patterns within the interview data. We found poor awareness and knowledge about mental illnesses, belief in faith and traditional healers, scarcity of resources (medicines, trained professionals and mental health inpatient and outpatient clinics), poor access to appropriate mental health facilities, and high costs for seeking mental health care. There is a critical gap between mental health related provisions in policy documents and its implementation at primary and district level.
Novel organoid construction strategy for non-involuting congenital hemangioma for drug validation
Authors: Wei Haoche , Li Yanan , Li Li , Hu Qian , Shi Mingsong , Cheng Linbo , Jiang Xile , Zhou Yanting , Chen Siyuan , Ji Yi , Chen Lijuan
Published: April 2023

Background

Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study.

Result

Here, we report a novel NICH organoid system construction and optimization process. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoids were human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids.

Conclusion

Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future.
Methodological and statistical approaches for the assessment of foot shape using three‐dimensional foot scanning: a scoping review
Authors: Allan Jamie J. , Munteanu Shannon E. , Bonanno Daniel R. , Buldt Andrew K. , Choppin Simon , Bullas Alice , Pearce Natalie , Menz Hylton B.
Published: April 2023

Objective

The objectives of this study were to: (i) review and provide a narrative synthesis of three‐dimensional (3D) foot surface scanning methodological and statistical analysis protocols, and (ii) develop a set of recommendations for standardising the reporting of 3D foot scanning approaches.

Methods

A systematic search of the SCOPUS, ProQuest, and Web of Science databases were conducted to identify papers reporting 3D foot scanning protocols and analysis techniques. To be included, studies were required to be published in English, have more than ten participants, and involve the use of static 3D surface scans of the foot. Papers were excluded if they reported two‐dimensional footprints only, 3D scans that did not include the medial arch, dynamic scans, or derived foot data from a full body scan.

Results

The search yielded 78 relevant studies from 17 different countries. The available evidence showed a large variation in scanning protocols. The subcategories displaying the most variation included scanner specifications (model, type, accuracy, resolution, capture duration), scanning conditions (markers, weightbearing, number of scans), foot measurements and definitions used, and statistical analysis approaches. A 16‐item checklist was developed to improve the consistency of reporting of future 3D scanning studies.

Conclusion

3D foot scanning methodological and statistical analysis protocol consistency and reporting has been lacking in the literature to date. Improved reporting of the included subcategories could assist in data pooling and facilitate collaboration between researchers. As a result, larger sample sizes and diversification of population groups could be obtained to vastly improve the quantification of foot shape and inform the development of orthotic and footwear interventions and products.
BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation
Authors: Liu Bin , Liu Yongjie , Li Shuman , Chen Pingping , Zhang Jun , Feng Liping
Published: April 2023

Background

Brain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive. In this study, we investigated the reproductive outcomes of BDNF treatment and potential mechanisms in aged mice.

Method

“Aged” mice (35–37 weeks old, n = 68) were treated with recombinant human BDNF protein (rhBDNF, 1 µg/200 µL) through daily intraperitoneal (IP) injection for 10 days with/without ovulation induction. Reproductive age mice (8–10 weeks old, n = 28) were treated with ANA 12 (a selective BDNF receptor, TrkB antagonist) through daily IP injection for 5 days with/without ovulation induction. Ovarian function was assessed by ovarian weight, number of follicles, and sex hormone productions. Following induction of ovulation, the number of total oocytes or abnormal oocytes, and blastocyst formation were assessed. Reproductive functions of the mice were evaluated, including pregnancy rate, mating duration for conception, implantation sites, litter size, and weight of offspring. Finally, the molecular mechanism of the effects of BDNF on ovarian cell functions in mice were examined by Western blot and immunofluorescence.

Results

rhBDNF treatment increased the ovarian weight, number of follicles, number and quality of oocytes including increased blastocysts formation, blood estrogen levels, and pregnancy rate in 35-37-week-old mice. Conversely, BDNF receptor antagonist, ANA 12, treatment decreased the ovarian volume and number of antral follicles and increased the proportion of abnormal oocytes in 8-10-week-old mice. We further demonstrated that BDNF treatment promoted ovarian cell proliferation as well as activation of TrkB and cyclinD1-creb signalling.

Conclusion

We demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.
Angiotensin-converting enzyme 2 in dogs with Dirofilaria immitis
Authors: Adin Darcy B. , Spalla Meaghan , Walden Heather , Gruntmeir Jeff , Hernandez Jorge A. , Long Maureen
Published: April 2023

Background

Infection by the canine heartworm, Dirofilaria immitis, causes significant cardiopulmonary disease, with progression impacted by increasing parasite numbers and duration of infection. The renin–angiotensin–aldosterone system (RAAS) is an important mediator of cardiac and pulmonary disease. Angiotensin-converting enzyme 2 (ACE2) mitigates the maladaptive effects of angiotensin II by converting it to angiotensin (1-7). We hypothesized that circulating ACE2 activity would be altered in dogs with high heartworm infection intensities relative to dogs without heartworms.

Methods

Frozen serum samples (−80 °C) from 30 dogs euthanized at Florida shelters were analyzed for ACE2 activity using liquid chromatography–mass spectrometry/mass spectroscopy and a kinetics approach with and without an ACE2 inhibitor. A convenience sample of 15 dogs without heartworms (HW0) and 15 dogs with > 50 heartworms (HW>50) was included. Heartworm number and microfilariae presence were determined at necropsy. The effects of heartworm status, body weight, and sex on ACE2 were evaluated using regression analysis. Values of P < 0.05 were considered significant.

Results

All HW0 dogs were D. immitis microfilariae-negative and all HW>50 dogs were D. immitis microfilariae-positive with a median adult worm count of 74 (minimum = 63, maximum = 137). The ACE2 activity of HW>50 dogs (median = 28.2 ng/ml; minimum = 13.6, maximum = 76.2) was not different from HW0 dogs (median 31.9 ng/ml; minimum = 14.1, maximum = 139.1; P = 0.53). The ACE2 activity was higher in dogs with high body weight (median 34.2 ng/ml minimum = 14.1, maximum = 76.2) than in dogs with low weight (median 27.5 ng/ml; minimum = 16.4, maximum = 139.1; P = .044).

Conclusions

Heartworm infection did not impact ACE2 activity in shelter dogs with or without heartworms, but heavier dogs had higher ACE2 activity compared to lighter dogs. Comprehensive RAAS evaluation and additional clinical information would aid in understanding how ACE2 activity relates to the entire cascade and clinical status in dogs with heartworm disease.

Graphical Abstract
Increasing temperature denatures canine IgG reducing its ability to inhibit heartworm antigen detection
Authors: Gruntmeir Jeff M. , Abbott Jeff R. , Kima Peter E. , Long Maureen T. , Blagburn Byron L. , Walden Heather S.
Published: April 2023

Background

Immune complexing of target antigen to high affinity host antibody is recognized to impact the sensitivity of commercial heartworm antigen tests. Published information describing the effect of heat on interfering canine host antibodies is lacking. Immune complex dissociation (ICD) by heat treatment of serum for samples initially testing negative for heartworm antigen increases sensitivity of commercial antigen tests, particularly for single sex or low adult infection intensities. In this study the stability and nature of the targeted epitope and mechanism of heat ICD were examined.

Methods

Canine IgG was isolated using protein-A columns from serum originating from four dogs evaluated after necropsy: one dog with evidence of previously cleared infection and three dogs with confirmed heartworm infections. These dogs were expected to have an excess of antibodies based on negative antigen test and to have no or low antigen optical density, respectively, following heat treatment. Interference of antigen detection on (non-heated) positive serum was evaluated, following 1:1 mixing of antibody/PBS solutions previously heated at 25 °C, 65 °C, 75 °C, 85 °C, 95 °C and 104 °C, compared to positive serum/PBS control measured by optical density using a commercial heartworm antigen ELISA and protein quantification. Live heartworms incubated in media for 72 h provided excretory/secretory antigen for antigen stability studies following heat, endopeptidase digestion and disulfide bond reduction.

Results

Mixing antigen-positive heartworm serum with antibody solutions demonstrated a significant inhibition of antigen detection for antibody solutions previously heated at 25 °C and 65 °C relative to positive serum/PBS control. Antigen detection optical density was restored at or above the control when positive serum was mixed with solutions previously heated at 75 °C, 85 °C, 95 °C and 104 °C. Significant changes occurred in protein levels for antibody solutions heated at 75 °C, 85 °C, 95 °C and 104 °C. Relative stability of antigen from live heartworms in culture was demonstrated following heat, chemical and enzymatic treatment.

Conclusions

Significant changes in protein levels and antigen binding ability occurred in IgG solutions heated above 65 °C. The findings confirm heat denaturation of antibodies as the suspected mechanism of heat ICD at 104 °C for antigen diagnosis of heartworm. No significant change occurred in antigen detection following heat, chemical or enzymatic digestions supporting a heat-stable linear nature of the epitope.

Graphical Abstract
Emerging role of bacterial outer membrane vesicle in gastrointestinal tract
Authors: Tian Cheng-mei , Yang Mei-feng , Xu Hao-ming , Zhu Min-zheng , Zhang Yuan , Yao Jun , Wang Li-sheng , Liang Yu-jie , Li De-feng
Published: April 2023

Bacteria form a highly complex ecosystem in the gastrointestinal (GI) tract. In recent years, mounting evidence has shown that bacteria can release nanoscale phospholipid bilayer particles that encapsulate nucleic acids, proteins, lipids, and other molecules. Extracellular vesicles (EVs) are secreted by microorganisms and can transport a variety of important factors, such as virulence factors, antibiotics, HGT, and defensive factors produced by host eukaryotic cells. In addition, these EVs are vital in facilitating communication between microbiota and the host. Therefore, bacterial EVs play a crucial role in maintaining the GI tract’s health and proper functioning. In this review, we outlined the structure and composition of bacterial EVs. Additionally, we highlighted the critical role that bacterial EVs play in immune regulation and in maintaining the balance of the gut microbiota. To further elucidate progress in the field of intestinal research and to provide a reference for future EV studies, we also discussed the clinical and pharmacological potential of bacterial EVs, as well as the necessary efforts required to understand the mechanisms of interaction between bacterial EVs and gut pathogenesis.
Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings
Authors: Beye Seydina Alioune , Diallo Boubacar , Keita Modibo , Cissoko Yacouba , Ouattara Khadidia , Dicko Hammadoun , Shabani Majaliwa , Sidibé Amadou , Berthé Modibo , Coulibaly Yaya Ibrahim , Diani Nouhoum , Keita Mohamed , Toloba Yacouba , Dao Sounkalo , Suttels Veronique , Coulibaly Youssouf , Mekontso Dessap Armand
Published: April 2023

Background

Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting.

Methods

We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings.

Results

The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of − 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients’ age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score.

Conclusion

Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.
Heterogeneous scene matching based on the gradient direction distribution field
Authors: Li Qingge , Lu Ruitao , Yang Xiaogang , Wang Siyu , Shen Tong , Xia Wenxin , Wei Zhaoying
Published: April 2023

Heterogeneous scene matching is a key technology in the field of computer vision. The image rotation problem is popular and difficult in the field of heterogeneous scene matching. In this paper, a heterogeneous scene matching method based on the gradient direction distribution field is proposed, and distributed field theory is introduced into heterogeneous scene matching for the first time. First, the distribution field of the gradient direction is constructed and fuzzified, and then the effective regions are selected. Then, the distribution field of the main direction is defined to solve the matching errors due to the existence of rotational transformations between heterogeneous source images. Third, the chi-square distance is introduced as a similarity measure. Finally, the hill-climbing method search strategy, which greatly improves the efficiency of the algorithm, is adopted. Experimental results on 8 pairs of infrared and visible heterogeneous images demonstrate that the proposed method outperforms the other state-of-the-art region-based matching methods in terms of the robustness, accuracy, and real-time performance.
Community—Minimal Invasive Tissue Sampling (cMITS) using a modified ambulance for ascertaining the cause of death: A novel approach piloted in a remote inaccessible rural area in India
Authors: Satav Ashish , Wairagkar Niteen , Khirwadkar Shubhada , Dani Vibhawari , Rasaily Reeta , Agrawal Usha , Thakar Yagnesh , Raje Dhananjay , Siraj Fouzia , Garge Pradyot , Palaskar Sameer , Kumbhare Shraddha , Simões Eric A. F.
Published: April 2023

Background

Melghat in India is a hilly, forested, difficult to access, impoverished rural area in northeast part of Maharashtra (Central India) with difficult healthcare access. Melghat has very high Mortality rates, because of grossly inadequate medical facilities. (1) Home deaths contribute to 67% of deaths,(2) which are difficult to track and where cause of death is mostly unknown.

Methods

A feasibility study was carried out in 93 rural villages and 5 hospitals to assess feasibility of tracking real-time community mortality and to ascertain cause of death in 0–60 months and 16–60 years age group using Minimal Invasive Tissue Sampling (MITS) in purpose-modified ambulance. We used the network of village health workers (VHW)s, to establish real-time community mortality tracking. Upon receipt of reports of home death, we performed MITS within 4 h of death in the vicinity of the village.

Results

We conducted 16 MITS. Nine, in MITS ambulance in community and seven at MAHAN hospital. The acceptance rate of MITS was 59.26%. Standard operating procedure (SOP) of conducting community MITS in an ambulance, is established. Major challenges were, Covid19 lockdown, reluctance of tribal parents for consent for MITS due to illiteracy, superstitions and fear of organ removal. Ambulance was an easy to reach transport means in remote area, provided a well-designed and discrete facility to perform MITS in community, winning the confidence of bereaved family. This has reduced time interval between time of death and performing MITS.

Conclusions

MITS in purpose-modified Ambulance can be used worldwide for community MITS especially in areas which are remote and lack healthcare access. This solution needs to be assessed in different cultural settings to document culture specific issues.
Adoption of improved rice technologies in major rice producing areas of Ethiopia: a multivariate probit approach
Authors: Assaye Abebaw , Habte Endeshaw , Sakurai Seiichi
Published: April 2023

Background

The need for adopting improved rice technologies and practices has become more important in Ethiopia as the national self-sufficiency gap has increased. This article examines the adoption level and factors governing the adoption of improved rice technology packages and practices using data collected from 594 rice-producing household heads in Ethiopia. A multivariate probit (MVP) model involving a system of five equations was used to assess the determinant for the decision to adopt improved rice technologies and practices.

Results

The results showed that the adoption levels of improved rice varieties, row planting, recommended rate of urea fertilizer, recommended rate of DAP/NPS fertilizer, and recommended weeding frequency was 24.4%, 23.4%, 40.9%, 38.6%, and 52.4%, respectively. The model results attested that improved rice production technology packages are complementary. This finding implies that farm-level policies that affect the use of one improved agricultural technology can have a positive effect on the other technologies. The various demographic, socioeconomic, and institutional variables were found to influence the decisions to adopt different technologies of improved rice technology packages with different signs.

Conclusions

Therefore, the government should devise ways to ease the accessibility of improved seeds and fertilizers along with the introduction of labor-saving technologies to promote row planting and achieve wider adoption of the technologies. Policies and interventions that are informed about such factors are required to accelerate the adoption of improved rice technology packages in Ethiopia to realize green revolution and secure self-sufficiency of rice sustainably.
The mediating role of early maladaptive schemas in the relationship between attachment styles and loneliness
Authors: Jalilian Kosar , Momeni Khodamorad , Jebraeili Hashem
Published: April 2023

Background

As with the increasing prevalence of loneliness among college students, it seems necessary to investigate the early grounds of its formation. Therefore, the present study was conducted to examine the relationship between attachment styles and loneliness through the mediating role of early maladaptive schemas (EMS).

Methods

This research was correlational, of structural equations modeling (SEM) type. The statistical population included all the college students of the universities of Kermanshah in the academic year 2020–2021, of whom 338 were selected using convenience sampling. The measures used in this study included DiTomasso et al.’s social and emotional loneliness of adults, Hazan and Shaver’s adult attachment, and Young’s schema scales. For data analysis, Pearson’s correlation coefficient and SEM were used in Lisrel 8.8 and SPSS-22 software.

Results

The results illustrated that the hypothesized model of the study has a good fit in the studied sample. It was also found that both the avoidant and ambivalent attachment styles are related to loneliness through two EMS of disconnection-rejection and other-directedness.

Conclusions

Based on the findings, measures are recommended to increase information regarding the basic and underlying factors affecting loneliness for therapists and psychological specialists.
Comparison of cardiac index measurements in intensive care patients using continuous wave vs. pulsed wave echo-Doppler compared to pulse contour cardiac output
Authors: Parulekar Prashant , Powys-Lybbe James , Bassett Paul , Roques Seb , Snazelle Mark , Millen Gemma , Harris Tim
Published: April 2023

Purpose

Cardiac index (CI) assessments are commonly used in critical care to define shock aetiology and guide resuscitation. Echocardiographic assessment is non-invasive and has high levels of agreement with thermodilution assessment of CI. CI assessment is derived from the velocity time integral (VTI) assessed using pulsed wave (PW) doppler at the level of the left ventricular outflow tract divided by body mass index. Continuous wave (CW) doppler through the aortic valve offers an alternative means to assess VTI and may offer better assessment at high velocities.

Methods

We performed a single centre, prospective, observational study in a 15-bed intensive care unit in a busy district general hospital. Patients had simultaneous measurements of cardiac index by Pulse Contour Cardiac Output (PiCCO) (thermodilution), transthoracic echocardiographic PW-VTI and CW-VTI. Mean differences were measured with Bland–Altman limits of agreement and percentage error (PE) calculations.

Results

Data were collected on 52 patients. 71% were supported with noradrenaline with or without additional inotropic or vasopressor agents. Mean CIs were: CW-VTI 2.7 L/min/m2 (range 0.78–5.11, SD 0.92). PW-VTI 2.33 L/min/m2 (range 0.77–5.40, SD 0.90) and PiCCO 2.86 L/min/m2 (range 1.50–5.56, SD 0.93). CW-VTI and PiCCO mean difference was − 0.16 L/min/m2 PE 43.5%. PW-VTI and PiCCO had a mean difference of − 0.54 L/min/m2 PE 38.6%. CW-VTI and PW-VTI had a mean difference of 0.38 L/min/m2 PE 46.0%.

Conclusions

CI derived from both CW-VTI and PW-VTI methods underestimate CI compared to PiCCO, with the CW-VTI method having closer values overall to PiCCO. CW-VTI may offer a more accurate assessment of CI. If using Critchley’s PE cutoff of 30%, none of the doppler methods may accurately reflect the actual cardiac index.
A systematic study on the use of multifunctional nanodiamonds for neuritogenesis and super-resolution imaging
Authors: Kim Jaeheung , Kang Moon Sung , Jun Seung Won , Jo Hyo Jung , Han Dong-Wook , Kim Chang-Seok
Published: April 2023

Background

Regeneration of defective neurons in central nervous system is a highlighted issue for neurodegenerative disease treatment. Various tissue engineering approaches have focused on neuritogenesis to achieve the regeneration of damaged neuronal cells because damaged neurons often fail to achieve spontaneous restoration of neonatal neurites. Meanwhile, owing to the demand for a better diagnosis, studies of super-resolution imaging techniques in fluorescence microscopy have triggered the technological development to surpass the classical resolution dictated by the optical diffraction limit for precise observations of neuronal behaviors. Herein, the multifunctional nanodiamonds (NDs) as neuritogenesis promoters and super-resolution imaging probes were studied.

Methods

To investigate the neuritogenesis-inducing capability of NDs, ND-containing growing medium and differentiation medium were added to the HT-22 hippocampal neuronal cells and incubated for 10 d. In vitro and ex vivo images were visualized through custom-built two-photon microscopy using NDs as imaging probes and the direct stochastic optical reconstruction microscopy (dSTORM) process was performed for the super-resolution reconstruction owing to the photoblinking properties of NDs. Moreover, ex vivo imaging of the mouse brain was performed 24 h after the intravenous injection of NDs.

Results

NDs were endocytosed by the cells and promoted spontaneous neuritogenesis without any differentiation factors, where NDs exhibited no significant toxicity with their outstanding biocompatibility. The images of ND-endocytosed cells were reconstructed into super-resolution images through dSTORM, thereby addressing the problem of image distortion due to nano-sized particles, including size expansion and the challenge in distinguishing the nearby located particles. Furthermore, the ex vivo images of NDs in mouse brain confirmed that NDs could penetrate the blood–brain barrier (BBB) and retain their photoblinking property for dSTORM application.

Conclusions

It was demonstrated that the NDs are capable of dSTORM super-resolution imaging, neuritogenic facilitation, and BBB penetration, suggesting their remarkable potential in biological applications.

Graphical Abstract
Why life expectancy over-predicts crude death rate
Authors: Liang Haili , Guo Zhen , Tuljapurkar Shripad
Published: April 2023

Life expectancy is widely used and reported; for example, the UN Human Development Index uses life expectancy as a key component. But many users of period life expectancy do not understand and interpret life expectancy as demographers do. In particular, period life expectancy almost always over-predicts the crude death rate. Indeed, in most observed populations, the annual deaths recorded are always less than one may expect in the corresponding stationary population. To explain this over-prediction, in this paper we analyze how deviations from stationarity affect the crude death rate. We use theory to show that small deviations from the stationary age structure (as high as 20% at each age) always lead to over-prediction. Then we examine global data to show that over-prediction is widespread, occurring even in populations where the deviation from stationarity is large. Finally, we show that populations around the world and over many decades have age structures that are almost always far from stationary (or indeed, stability). But we also show that the deviation is often due to the demographic transition, with population bulges at the middle ages where mortality is low.
Impact of Artificial Intelligence System and Volumetric Density on Risk Prediction of Interval, Screen-Detected, and Advanced Breast Cancer
Authors: Vachon Celine M. , Scott Christopher G. , Norman Aaron D. , Khanani Sadia A. , Jensen Matthew R. , Hruska Carrie B. , Brandt Kathleen R. , Winham Stacey J. , Kerlikowske Karla
Published: April 2023

PURPOSE

Artificial intelligence (AI) algorithms improve breast cancer detection on mammography, but their contribution to long-term risk prediction for advanced and interval cancers is unknown.

METHODS

We identified 2,412 women with invasive breast cancer and 4,995 controls matched on age, race, and date of mammogram, from two US mammography cohorts, who had two-dimensional full-field digital mammograms performed 2-5.5 years before cancer diagnosis. We assessed Breast Imaging Reporting and Data System density, an AI malignancy score (1-10), and volumetric density measures. We used conditional logistic regression to estimate odds ratios (ORs), 95% CIs, adjusted for age and BMI, and C-statistics (AUC) to describe the association of AI score with invasive cancer and its contribution to models with breast density measures. Likelihood ratio tests (LRTs) and bootstrapping methods were used to compare model performance.

RESULTS

On mammograms between 2-5.5 years prior to cancer, a one unit increase in AI score was associated with 20% greater odds of invasive breast cancer (OR, 1.20; 95% CI, 1.17 to 1.22; AUC, 0.63; 95% CI, 0.62 to 0.64) and was similarly predictive of interval (OR, 1.20; 95% CI, 1.13 to 1.27; AUC, 0.63) and advanced cancers (OR, 1.23; 95% CI, 1.16 to 1.31; AUC, 0.64) and in dense (OR, 1.18; 95% CI, 1.15 to 1.22; AUC, 0.66) breasts. AI score improved prediction of all cancer types in models with density measures ( PLRT values < .001); discrimination improved for advanced cancer (ie, AUC for dense volume increased from 0.624 to 0.679, Δ AUC 0.065, P = .01) but did not reach statistical significance for interval cancer.

CONCLUSION

AI imaging algorithms coupled with breast density independently contribute to long-term risk prediction of invasive breast cancers, in particular, advanced cancer.
Dose-Escalated Radiotherapy Alone or in Combination With Short-Term Androgen Deprivation for Intermediate-Risk Prostate Cancer: Results of a Phase III Multi-Institutional Trial
Authors: Krauss Daniel J. , Karrison Theodore , Martinez Alvaro A. , Morton Gerard , Yan Di , Bruner Deborah Watkins , Movsas Benjamin , Elshaikh Mohamed , Citrin Deborah , Hershatter Bruce , Michalski Jeff M. , Efstathiou Jason Alexander , Currey Adam , Kavadi Vivek S. , Cury Fabio L. , Lock Michael , Raben Adam , Seaward Samantha Andrews , El-Gayed Ali , Rodgers Joseph P. , Sandler Howard M.
Published: April 2023

PURPOSE

It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT).

METHODS

The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy.

RESULTS

Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P <.001), DM (HR, 0.25; P <.001), PCSM (HR, 0.10; P = .007), and salvage therapy use (HR, 0.62; P = .025). Other-cause deaths were not significantly different ( P = .56). Acute grade ≥3 adverse events (AEs) occurred in 2% of patients in arm 1 and in 12% for arm 2 ( P <.001). Cumulative incidence of late grade ≥3 AEs was 14% in arm 1 and 15% in arm 2 ( P = .29).

CONCLUSION

STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.