bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized phase II trial of MRI-guided salvage radiotherapy for prostate cancer in 4 weeks versus 2 weeks (SHORTER)
Authors: Marciscano Ariel E. , Wolfe Sydney , Zhou Xi Kathy , Barbieri Christopher E. , Formenti Silvia C. , Hu Jim C. , Molina Ana M. , Nanus David M. , Nauseef Jones T. , Scherr Douglas S. , Sternberg Cora N. , Tagawa Scott T. , Nagar Himanshu
Published: August 2023

Background

Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment.

Methods

A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival.

Discussion

The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions.

Trial registration

ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.
Abnormalities of the Amygdala in schizophrenia: a real world study
Authors: Zheng Guangen , Zhou Yang , Zhou Jieming , Liang Shuting , Li Xiaoling , Xu Caixia , Xie Guojun , Liang Jiaquan
Published: August 2023

Background

Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area.

Methods

We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People’s Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment.

Results

Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p’ = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover.

Conclusion

There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.
Association between alcohol consumption and risk of stroke among adults: results from a prospective cohort study in Chongqing, China
Authors: Liu Xin , Ding Xianbin , Zhang Fan , Chen Liling , Luo Qinwen , Xiao Meng , Liu Xiang , Wu Yunyun , Tang Wenge , Qiu Jingfu , Tang Xiaojun
Published: August 2023

Background

The incidence of stroke in China is increasing, along with a clear trend in the prevalence of risk factors. Alcohol consumption is also a risk factor for stroke. Many cohort studies have explored the relationship between alcohol consumption and stroke risk. However, findings have been inconsistent.

Methods

We used cluster sampling to select 13 districts and counties (at the same level) in Chongqing, China. Then, we used stratified random sampling to distribute the number of people in each district and county. 23,308 adults aged 30–79 were recruited between October 2018 and February 2019. Follow-up was conducted through a monitoring system and questionnaires until September 2022. Information on alcohol consumption and other covariates was collected using a standardized questionnaire. Participants were asked to report their weekly frequency of drinking over the past year and weekly intake of various alcoholic beverages in general. The frequency of drinking was divided into three categories: 1–2 d/week, 3–5 d/week, and 6–7 d/week. The average daily alcohol consumption is calculated based on the amount of alcohol contained in different alcoholic beverages. It is classified as nondrinker (0 g/day), light (0 to 12 g/day), moderate (13 to 36 g/day), and high (> 36 g/day). Cox proportional hazard regression models were used to estimate the association between alcohol consumption and stroke risk. Results are shown as multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

With an average follow-up of 3.80 years, there were 310 new stroke events. The incidence of total stroke was 368.69 per 100,000 person-years. Overall, after adjusting for covariates, moderate alcohol consumption (average daily alcohol consumption 13–36 g/d) was associated with a lower risk of total stroke (HR: 0.48; 95% CI: 0.25–0.92) compared with nondrinkers. The adjusted HR and 95% CI for total stroke and ischemic stroke for those who drank alcohol 6–7 days per week were 0.60(0.37, 0.96) and 0.53(0.30, 0.94), respectively. The risk of total stroke (HR: 0.39; 95% CI: 0.17–0.89) was reduced in a pattern of drinking 6–7 days per week but with a mean alcohol consumption of less than 36 g/d. There was no significant association between alcohol consumption and hemorrhagic stroke.

Conclusion

This study suggests moderate alcohol consumption is associated with a lower risk of total stroke. And healthy drinking patterns should be of more significant concern.
Spatiotemporal dynamics of cholera in the Democratic Republic of the Congo before and during the implementation of the Multisectoral Cholera Elimination Plan: a cross-sectional study from 2000 to 2021
Authors: Taty Nadège , Bompangue Didier , de Richemond Nancy Meschinet , Muyembe JJ
Published: August 2023

Background

The Democratic Republic of the Congo (DRC) implemented the first strategic Multisectoral Cholera Elimination Plan (MCEP) in 2008–2012. Two subsequent MCEPs have since been implemented covering the periods 2013–2017 and 2018–2021. The current study aimed to assess the spatiotemporal dynamics of cholera over the recent 22-year period to determine the impact of the MCEPs on cholera epidemics, establish lessons learned and provide an evidence-based foundation to improve the implementation of the next MCEP (2023–2027).

Methods

In this cross-sectional study, secondary weekly epidemiological cholera data covering the 2000–2021 period was extracted from the DRC Ministry of Health surveillance databases. The data series was divided into four periods: pre-MCEP 2003–2007 (pre-MCEP), first MCEP (MCEP-1), second MCEP (MCEP-2) and third MCEP (MCEP-3). For each period, we assessed the overall cholera profiles and seasonal patterns. We analyzed the spatial dynamics and identified cholera risk clusters at the province level. We also assessed the evolution of cholera sanctuary zones identified during each period.

Results

During the 2000–2021 period, the DRC recorded 520,024 suspected cases and 12,561 deaths. The endemic provinces remain the most affected with more than 75% of cases, five of the six endemic provinces were identified as risk clusters during each MCEP period (North Kivu, South Kivu, Tanganyika, Haut-Lomami and Haut-Katanga). Several health zones were identified as cholera sanctuary zones during the study period: 14 health zones during MCEP-1, 14 health zones during MCEP-2 and 29 health zones during MCEP-3. Over the course of the study period, seasonal cholera patterns remained constant, with one peak during the dry season and one peak during the rainy season.

Conclusion

Despite the implementation of three MCEPs, the cholera context in the DRC remains largely unchanged since the pre-MCEP period. To better orient cholera elimination activities, the method used to classify priority health zones should be optimized by analyzing epidemiological; water, sanitation and hygiene; socio-economic; environmental and health indicators at the local level. Improvements should also be made regarding the implementation of the MCEP, reporting of funded activities and surveillance of cholera cases. Additional studies should aim to identify specific bottlenecks and gaps in the coordination and strategic efforts of cholera elimination interventions at the local, national and international levels.
Influence of ultrasound machine settings on quantitative measures derived from spatial frequency analysis of muscle tissue
Authors: Crawford Scott K. , Kliethermes Stephanie A. , Heiderscheit Bryan C. , Bashford Greg R.
Published: August 2023

Background

Ultrasound is a powerful tool for diagnostic purposes and provides insight into both normal and pathologic tissue structure. Spatial frequency analysis (SFA) methods characterize musculoskeletal tissue organization from ultrasound images. Both sonographers in clinical imaging and researchers may alter a minimized range of ultrasound settings to optimize image quality, and it is important to know how these small adjustments of these settings affect SFA parameters. The purpose of this study was to investigate the effects of making small adjustments in a typical default ultrasound machine setting on extracted spatial frequency parameters (peak spatial frequency radius (PSFR), Mmax, Mmax%, and Sum) in the biceps femoris muscle.

Methods

Longitudinal B-mode images were collected from the biceps femoris muscle in 36 participants. The window depth, foci locations, and gain were systematically adjusted consistent with clinical imaging procedures for a total of 27 images per participant. Images were analyzed by identifying a region of interest (ROI) in the middle portion of the muscle belly in a template image and using a normalized two-dimensional cross-correlation technique between the template image and subsequent images. The ROI was analyzed in the frequency domain using conventional SFA methods. Separate linear mixed effects models were run for each extracted parameter.

Results

PSFR was affected by modifications in focus location only (p < 0.001) with differences noted between all locations. Mmax% was influenced by the interaction of gain and focus location (p < 0.001) but was also independently affected by increasing window depth (p < 0.001). Both Mmax and Sum parameters were sensitive to small changes in machine settings with the interaction of focus location and window depth (p < 0.001 for both parameters) as well as window depth and gain (p < 0.001 for both) influencing the extracted values.

Conclusions

Frequently adjusted imaging settings influence some SFA statistics. PSFR and Mmax% appear to be most robust to small changes in image settings, making them best suited for comparison across individuals and between studies, which is appealing for the clinical utility of the SFA method.
Changes in relationships, HIV risk, and feelings towards PrEP: findings from a qualitative explanatory study among participants in the CHARISMA intervention trial
Authors: Hartmann Miriam , Triplett Noah , Roberts Sarah T. , Lanham Michele , Reddy Krishnaveni , Tenza Siyanda , Mayisela Nonkululeko , Mbewe Dorica , Maboa Ontathile , Mampuru Lydia , Tolley Elizabeth E. , Palanee-Phillips Thesla , Montgomery Elizabeth T.
Published: August 2023

Background

Intimate partner violence (IPV) and other relationship-based challenges have been demonstrated to reduce women’s ability to use pre-exposure prophylaxis (PrEP) effectively for HIV prevention. The Community Health Clinical Model for Agency in Relationships and Safer Microbicide Adherence (CHARISMA) intervention was designed to mitigate these challenges and increase South African women’s agency to use PrEP. The CHARISMA randomized controlled trial did not identify statistically significant differences in PrEP adherence or relationship dynamics between the intervention and control arms. As such, the aim of this explanatory qualitative sub-study was to understand women’s experiences with the CHARISMA trial and explore reasons for the null results.

Methods

Twelve CHARISMA trial participants were purposively selected to participate in serial in-depth interviews, which took place at the trial end and 3 months later. Participants represented individuals who had received each of the three counselling modules, 1) healthy communication counselling, 2) PrEP disclosure counselling, or 3) IPV counselling, as well as those in the control arm who received IPV standard-of-care counselling.

Results

A thematic case analysis revealed numerous positive relationship outcomes among intervention participants, including identifying and ending unhealthy relationships, gaining a sense of personal empowerment, and enacting more positive behaviors and HIV risk reduction strategies in subsequent relationships. These positive shifts were occasionally described as contributing to decisions to discontinue PrEP use, which may partly explain the limited impact of the intervention on PrEP adherence.

Conclusions

Future investigations of counselling interventions addressing relationship-based barriers to PrEP use should account for changing risk dynamics and need for PrEP.
The development of practice standards for patient education in nurse-led clinics: a mixed-method study
Authors: Pouresmail Zohre , Nabavi Fatemeh Heshmati , Rassouli Maryam
Published: August 2023

Introduction

Educating patients and families about self-care is one of the important roles of nurses in Nurse-led clinics (NLCs). NLCs need standards for guiding the practice of nurses. A standard is an authoritative statement that sets out the legal and professional basis of nursing practice. This paper seeks to report the development of practice standards for patient and family education in NLCs.

Methods

This project used a Sequential-Exploratory mixed methods design. Before the study, we conducted a literature review to identify gaps. Directed content analysis was used in phase 1. The second phase involved two focus groups. The third phase involves two rounds of modified Delphi.

Results

Twenty-nine participants were interviewed, and 1816 preliminary codes were formed in phase 1. 95 standards were grouped into three main categories (structure, process, and outcome). In the first focus group, experts eliminate 32 standards. Experts eliminate 8 standards after the second stage of the focus group. After two rounds of Delphi, the final version of the standard consists of 46 standards (13 structure, 28 process and 5 outcome).

Conclusions

Nurses and institutions could benefit from practice standards for patient education in the NLCs, which consist of 46 statements in three domains, as a guide for clinical activities and a tool to gauge the quality of patient education in NLCs. The developed standards in this study can guide new and existing NLCs and help them evaluate ongoing activities. Providing patient education in NLCs based on standards can improve patients’ outcomes and promote their health.
miRDM-rfGA: Genetic algorithm-based identification of a miRNA set for detecting type 2 diabetes
Authors: Park Aron , Nam Seungyoon
Published: August 2023

Background

Type 2 diabetes mellitus (T2DM) affects approximately 451 million adults globally. In this study, we identified the optimal combination of marker candidates for detecting T2DM using miRNA-Seq data from 95 samples including T2DM and healthy individuals.

Methods

We utilized the genetic algorithm (GA) in the discovery of an optimal miRNA biomarker set. We discovered miRNA subsets consisting of three miRNAs for detecting T2DM by random forest-based GA (miRDM-rfGA) as a feature selection algorithm and created six GA parameter settings and three settings using traditional feature selection methods (F-test and Lasso). We then evaluated the prediction performance to detect T2DM in the miRNA subsets derived from each setting.

Results

The miRNA subset in setting 5 using miRDM-rfGA performed the best in detecting T2DM (mean AUROC = 0.92). Target mRNA identification and functional enrichment analysis of the best miRNA subset (hsa-miR-125b-5p, hsa-miR-7-5p, and hsa-let-7b-5p) validated that this combination was involved in T2DM. We also confirmed that the targeted genes were negatively correlated with the clinical variables related to T2DM in the BxD mouse genetic reference population database.

Conclusions

Using GA in miRNA-Seq data, we identified the optimal miRNA biomarker set for T2DM detection. GA can be a useful tool for biomarker discovery and drug-target identification.
Predicting balance impairments in older adults: a wavelet-based center of pressure classification approach
Authors: Jafari Hedyeh , Gustafsson Thomas , Nyberg Lars , Röijezon Ulrik
Published: August 2023

Background

Aging is associated with a decline in postural control and an increased risk of falls. The Center of Pressure (CoP) trajectory analysis is a commonly used method to assess balance. In this study, we proposed a new method to identify balance impairments in older adults by analyzing their CoP trajectory frequency components, sensory inputs, reaction time, motor functions, and Fall-related Concerns (FrC).

Methods

The study includes 45 older adults aged $$75.2 (\pm 4.5)$$

75.2
(
±
4.5
)

years who were assessed for sensory and motor functions. FrC and postural control in a quiet stance with open and closed eyes on stable and unstable surfaces. A Discrete Wavelet Transform (DWT) was used to detect features in frequency scales, followed by the K-means algorithm to detect different clusters. The multinomial logistic model was used to identify and predict the association of each group with the sensorimotor tests and FrC.

Results

The study results showed that by DWT, three distinct groups of subjects could be revealed. Group 2 exhibited the broadest use of frequency scales, less decline in sensorimotor functions, and lowest FrC. The study also found that a decline in sensorimotor functions and fall-related concern may cause individuals to rely on either very low-frequency scales (group 1) or higher-frequency scales (group 3) and that those who use lower-frequency scales (group 1) can manage their balance more successfully than group 3.

Conclusions

Our study provides a new, cost-effective method for detecting balance impairments in older adults. This method can be used to identify people at risk and develop interventions and rehabilitation strategies to prevent falls in this population.
The socioeconomic distribution of life expectancy and healthy life expectancy in Chile
Authors: Espinoza Manuel Antonio , Severino Rodrigo , Balmaceda Carlos , Abbott Tomas , Cabieses Baltica
Published: August 2023

Background

Life expectancy (LE) has usually been used as a metric to monitor population health. In the last few years, metrics such as Quality-Adjusted-Life-Expectancy (QALE) and Health-Adjusted-Life- Expectancy (HALE) have gained popularity in health research, given their capacity to capture health related quality of life, providing a more comprehensive approach to the health concept. We aimed to estimate the distribution of the LE, QALEs and HALEs across Socioeconomic Status in the Chilean population.

Methods

Based on life tables constructed using Chiang II´s method, we estimated the LE of the population in Chile by age strata. Probabilities of dying were estimated from mortality data obtained from national registries. Then, life tables were stratified into five socioeconomic quintiles, based on age-adjusted years of education (pre-school, early years to year 1, primary level, secondary level, technical or university). Quality weights (utilities) were estimated for age strata and SES, using the National Health Survey (ENS 2017). Utilities were calculated using the EQ-5D data of the ENS 2017 and the validated value set for Chile. We applied Sullivan´s method to adjust years lived and convert them into QALEs and HALEs.

Results

LE at birth for Chile was estimated in 80.4 years, which is consistent with demographic national data. QALE and HALE at birth were 69.8 and 62.4 respectively. Men are expected to live 6.1% less than women. However, this trend is reversed when looking at QALEs and HALEs, indicating the concentration of higher morbidity in women compared to men. The distribution of all these metrics across SES showed a clear gradient in favour of a better-off population-based on education quintiles. The absolute and relative gaps between the lowest and highest quintile were 15.24 years and 1.21 for LE; 18.57 HALYs and 1.38 for HALEs; and 21.92 QALYs and 1.41 for QALEs. More pronounced gradients and higher gaps were observed at younger age intervals.

Conclusion

The distribution of LE, QALE and HALEs in Chile shows a clear gradient favouring better-off populations that decreases over people´s lives. Differences in LE favouring women contrast with differences in HALEs and QALEs which favour men, suggesting the need of implementing gender-focused policies to address the case-mix complexity. The magnitude of inequalities is greater than in other high-income countries and can be explained by structural social inequalities and inequalities in access to healthcare.
Novel prognostic gene signature for pancreatic ductal adenocarcinoma based on hypoxia
Authors: Ren Min , Feng Liaoliao , Zong Rongrong , Sun Huiru
Published: August 2023

Background

Currently, there is lack of marker to accurately assess the prognosis of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). This study aims to establish a hypoxia-related risk scoring model that can effectively predict the prognosis and chemotherapy outcomes of PDAC patients.

Methods

Using unsupervised consensus clustering algorithms, we comprehensively analyzed The Cancer Genome Atlas (TCGA) data to identify two distinct hypoxia clusters and used the weighted gene co-expression network analysis (WGCNA) to examine gene sets significantly associated with these hypoxia clusters. Then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used to construct a signature and its efficacy was evaluated using the International Cancer Genome Consortium (ICGC) PDAC cohort. Further, the correlation between the risk scores obtained from the signature and carious clinical, pathological, immunophenotype, and immunoinfiltration factors as well as the differences in immunotherapy potential and response to common chemotherapy drugs between high-risk and low-risk groups were evaluated.

Results

From a total of 8 significantly related modules and 4423 genes, 5 hypoxia-related signature genes were identified to construct a risk model. Further analysis revealed that the overall survival rate (OS) of patients in the low-risk group was significantly higher than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk scoring signature was an independent factor for prognosis prediction. Analysis of immunocyte infiltration and immunophenotype showed that the immune score and the anticancer immune response in the high-risk were significantly lower than that in the low-risk group.

Conclusion

The constructed hypoxia-associated prognostic signature demonstrated could be used as a potential risk classifier for PDAC.
Biomass smoke inhalation promotes neuroinflammatory and metabolomic temporal changes in the hippocampus of female mice
Authors: Scieszka David , Jin Yan , Noor Shahani , Barr Ed , Garcia Marcus , Begay Jessica , Herbert Guy , Hunter Russell P. , Bhaskar Kiran , Kumar Rahul , Gullapalli Rama , Bolt Alicia , McCormick Mark A. , Bleske Barry , Gu Haiwei , Campen Matthew J.
Published: August 2023

Smoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the temporal dynamics of neuroinflammation and metabolomics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6 J mice were exposed to wood smoke every other day for 2 weeks at an average exposure concentration of 0.5 mg/m3. Subsequent serial euthanasia occurred at 1-, 3-, 7-, 14-, and 28-day post-exposure. Flow cytometry of right hemispheres revealed two endothelial populations of CD31Hi and CD31Med expressors, with wood smoke inhalation causing an increased proportion of CD31Hi. These populations of CD31Hi and CD31Med were associated with an anti-inflammatory and pro-inflammatory response, respectively, and their inflammatory profiles were largely resolved by the 28-day mark. However, activated microglial populations (CD11b+/CD45low) remained higher in wood smoke-exposed mice than controls at day 28. Infiltrating neutrophil populations decreased to levels below controls by day 28. However, the MHC-II expression of the peripheral immune infiltrate remained high, and the population of neutrophils retained an increased expression of CD45, Ly6C, and MHC-II. Utilizing an unbiased approach examining the metabolomic alterations, we observed notable hippocampal perturbations in neurotransmitter and signaling molecules, such as glutamate, quinolinic acid, and 5-α-dihydroprogesterone. Utilizing a targeted panel designed to explore the aging-associated NAD+ metabolic pathway, wood smoke exposure drove fluctuations and compensations across the 28-day time course, ending with decreased hippocampal NAD+ abundance on day 28. Summarily, these results indicate a highly dynamic neuroinflammatory environment, with potential resolution extending past 28 days, the implications of which may include long-term behavioral changes, systemic and neurological sequalae directly associated with wildfire smoke exposure.
How is the implementation of empirical research results documented in conflict-affected settings? Findings from a scoping review of peer-reviewed literature
Authors: Leresche Enrica , Hossain Mazeda , De Rubeis Maria Livia , Hermans Veerle , Burtscher Doris , Rossi Rodolfo , Lonsdale Cordelia , Singh Neha S.
Published: August 2023

Implementation science scholars argue that knowing ‘what works’ in public health is insufficient to change practices, without understanding ‘how’, ‘where’ and ‘why’ something works. In the peer reviewed literature on conflict-affected settings, challenges to produce research, make decisions informed by evidence, or deliver services are documented, but what about the understanding of ‘how’, ‘where’ and ‘why’ changes occur? We explored these questions through a scoping review of peer-reviewed literature based on core dimensions of the Extended Normalization Process Theory. We selected papers that provided data on how something might work (who is involved and how?), where (in what organizational arrangements or contexts?) and why (what was done?). We searched the Global Health, Medline, Embase databases. We screened 2054 abstracts and 128 full texts. We included 22 papers (of which 15 related to mental health interventions) and analysed them thematically. We had the results revised critically by co-authors experienced in operational research in conflict-affected settings. Using an implementation science lens, we found that: (a) implementing actors are often engaged after research is produced to discuss feasibility; (b) new interventions or delivery modalities need to be flexible; (c) disruptions affect how research findings can lead to sustained practices; (d) strong leadership and stable resources are crucial for frontline actors; (e) creating a safe learning space to discuss challenges is difficult; (f) feasibility in such settings needs to be balanced. Lastly, communities and frontline actors need to be engaged as early as possible in the research process. We used our findings to adapt the Extended Normalization Process Theory for operational research in settings affected by conflicts. Other theories used by researchers to document the implementation processes need to be studied further.
Iguratimod suppresses Tfh cell differentiation in primary Sjögren’s syndrome patients through inhibiting Akt/mTOR/STAT3 signaling
Authors: Lyu Taibiao , Jiang Hui , Zeng Liuting , Liu Suying , He Chengmei , Luo Chaowen , Qiao Lin , Zhao Yan , Chen Hua
Published: August 2023

Background

Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren’s syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients.

Methods

We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation.

Results

Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation.

Conclusions

IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.
Gorham–Stout syndrome, the challenge in diagnosis and unique in treatment: a case report
Authors: Saberi Sadegh , Bagheri Nima , Kalantar Seyyed Hadi , Saffar Hana , Khabiri Seyyed Saeed
Published: August 2023

Background

Gorham–Stout disease is a rare condition with fewer than 400 reported cases in the literature. The presentation of Gorham–Stout disease varies on the basis of location, extent, fracture, and accompanying symptoms. It lacks a specific histopathological appearance but is characterized by vascular changes and the absence of cellular atypia.

Case presentation

This article presents a case study of a 16-year-old Persian boy with an entire femur with Gorham–Stout disease, highlighting the difficulties in managing this condition. The lack of a clear diagnosis resulted in prolonged procedures, delayed medical treatments, and ultimately required total femoral replacement with an endoprosthesis.

Conclusion

It is important to note that raising awareness of this disease and its potential complications can facilitate timely and appropriate treatment for patients presenting in the early stages of the disease.
A systematic review and meta-analysis of the effects of non-pharmacological interventions on quality of life in adults with multiple sclerosis
Authors: Gitman Victor , Moss Kasey , Hodgson David
Published: August 2023

Background

Multiple Sclerosis (MS) is a chronic debilitating disease that targets the central nervous system. Globally it is estimated that 2.8 million people live with MS (2018) and as there is no known cure; therefore, identifying methods to increase a patient’s quality of life (QoL) is of considerable importance. Non-pharmacological interventions are a viable and effective option to increase QoL in patients with MS, however, to date, the literature lacks a complete systematic review of these interventions.

Methods

A literature search was conducted for studies published up until March 4th 2022 in Scopus, Web of Science, CINAHL Plus, The Cochrane Library, Medline, and Embase. Studies were included if they were randomized control trials (RCTs) assessing a non-pharmacological intervention in adults with MS and measured QoL using the MSQOL-54, SF-36 or MSQLI tools for at least two time points. Quality assessment of each study was completed as well as a review of publication bias. Where possible, meta-analysis was conducted using a random effects model and for other studies a qualitative synthesis was presented.

Results

Thirty studies were included in the meta-analysis and eleven studies were summarized qualitatively. The pooled effects across all non-pharmacological interventions showed a modest improvement in both the physical and mental components of QoL, with a standardized mean difference (SMD) of 0.44 (95% CI 0.26–0.61) and 0.42 (95% CI 0.24–0.60), respectively. Non-pharmacological interventions based around a physical activity were found to be particularly effective in improving both the physical composite score (PCS) and mental composite score (MCS), with an SMD of 0.40 (95% CI 0.14–0.66) and 0.31 (95% CI 0.08–0.55), respectively. Interventions incorporating balance exercises presented a significant advantageous solution for improving QoL, with an SMD of 1.71 (95% CI 1.22, 2.20) and 1.63(95% CI 1.15–2.12) for PCS and MCS respectively.

Conclusions

This systematic review and meta-analysis identified that non-pharmacological interventions can be an effective method of improving QoL in patients with MS, especially modalities with a physical activity component and balance interventions.
Emergency contraceptive use of Metronidazole among University female students in Dodoma region of Tanzania: a descriptive cross-sectional study
Authors: Samson Nipael M. , Sumari Emmanuel Izack , Ndesendo Valence , Mbwasi Romuald
Published: August 2023

Background

Metronidazole is known for its therapeutic effect as antibacterial and anti-parasitic. However, its toxicity on the reproductive system remains unclear. Metronidazole use in rodents is associates with toxic effects on the reproductive system, including hormonal alterations, reduced number of fertile cells and reduced sites for implantation, size of the placental disc area, constituent elements of the labyrinth, and spongiotrophoblast layers. Its use at a therapeutic dose among humans has been associated with an increased risk of spontaneous abortion. The effects on the reproductive system in humans may result in misconceptions about contraceptive effects hence sexually active individuals like students who, for any reason, fail to access safe contraceptive services use any possible methods to protect them from conception. This study aims to investigate the unofficial (un-prescribed) use of Metronidazole as an emergency contraceptive and some of its associated factors.

Methods

This quantitative cross-sectional study involved 470 participants where stratified random sampling technique was used to obtain the sample from three educational institutions in the Dodoma Municipal, Dodoma region. Collected data were analyzed using SPSS version 25, descriptive statistical analysis was done to determine frequencies, percentages, and association, p < 0.05 was used to determine statistical significance. Further analysis using Multivariate binary logistic regression was done to determine the nature of the association between the study variables.

Results

The finding shows that 169(62.4%) use Metronidazole as an emergency contraceptive. Notably, 345(73.4%) stated that they had ever heard someone use Metronidazole for contraception, especially their peers. Furthermore, an increase in the year of study was significantly associated with reduced use of Metronidazole as an emergency contraceptive (B = [-0.45], p = [0.02]). Furthermore, an increase in age, studying in non-medical college/university, the experience of using contraceptive methods, and hearing someone ever used Metronidazole was found to be positively associated with its use as an emergency contraceptive, although not statistically significant.

Conclusion

Metronidazole was found to be used as an emergency contraceptive in high doses, different factors associated with its use, and reasons influencing its use. Further research may be done to explore the toxicological effect of high doses of Metronidazole as a contraception and compare the efficiency of Metronidazole over other emergency contraceptives.
Characterization of Somatotrope Cell Expansion in Response to GHRH in the Neonatal Mouse Pituitary
Authors: Gonigam Richard L , Weis Karen E , Ge Xiyu , Yao Boyuan , Zhang Qilin , Raetzman Lori T
Published: August 2023

In humans and mice, loss-of-function mutations in growth hormone–releasing hormone receptor (GHRHR) cause isolated GH deficiency. The mutant GHRHR mouse model, GhrhrLit/Lit (LIT), exhibits loss of serum GH, but also fewer somatotropes. However, how loss of GHRH signaling affects expansion of stem and progenitor cells giving rise to GH-producing cells is unknown. LIT mice and wild-type littermates were examined for differences in proliferation and gene expression of pituitary lineage markers by quantitative reverse transcription polymerase chain reaction and immunohistochemistry at postnatal day 5 (p5) and 5 weeks. At p5, the LIT mouse shows a global decrease in pituitary proliferation measured by proliferation marker Ki67 and phospho-histone H3. This proliferative defect is seen in a pituitary cell expressing POU1F1 with or without GH. SOX9-positive progenitors show no changes in proliferation in p5 LIT mice. Additionally, the other POU1F1 lineage cells are not decreased in number; rather, we observe an increase in lactotrope cell population as well as messenger RNA for Tshb and Prl. In the 5-week LIT pituitary, the proliferative deficit in POU1F1-expressing cells observed neonatally persists, while the number and proliferative proportion of SOX9 cells do not appear changed. Treatment of cultured pituitary explants with GHRH promotes proliferation of POU1F1-expressing cells, but not GH-positive cells, in a mitogen-activated protein kinase–dependent manner. These findings indicate that hypothalamic GHRH targets proliferation of a POU1F1-positive cell, targeted to the somatotrope lineage, to fine tune their numbers.
Introduction
Authors: Seigworth Gregory J. , Pedwell Carolyn
Published: August 2023

This introduction works to shape the sense of affect inquiry as a multivalent field of study. Whereas the first volume's introduction was titled “An Inventory of Shimmers,” this collection advances a “Shimmer of Inventories”—in other words, it argues for an affect theory that is as contingent to its situation, flexible in its disciplinary orientation, and rigorous in attending to the particularities of intensive encounters. The introduction offers some guidance about the practices of affect study and its unique take on the relationship of theory and practice. It also overviews the themes that organize the book's sections and their chapters.
Ο επιτάφιος λόγος του Θεόδωρου Στουδίτη στον Πλάτωνα Σακκουδίου (BHG 1553)
Authors: Πετρουγάκη Δέσποινα
Published: August 2023

Αντικείμενο αυτής της διατριβής αποτελεί η κριτική έκδοση του αφιερωμένου λόγου του Θεοδώρου Στουδίτη στον θείο και πνευματικό του πατέρα, Πλάτωνα Σακκουδίου, με ιστορικό πλαίσιο την περίοδο του μοιχικού σχίσματος και της Εικονομαχίας. Η έκδοση βασίζεται σε όλους τους γνωστούς μάρτυρες της χειρόγραφης παράδοσης του κειμένου (Patmiacus 254, Parisinus gr. 1197, Barberinianus gr. 533, Vaticanus gr. 1890, Vaticanus gr. 1660). Επιπρόσθετα διερευνάται η γλώσσα και το ύφος του κειμένου, το λογοτεχνικό είδος και η συμβολή του στη διαμόρφωση της πολύπτυχης αγιολογικής βιογραφίας της μέσης βυζαντινής περιόδου. Στον σχολιασμό διευκρινίζονται προσωπογραφικά στοιχεία, καθορίζονται γεωγραφικά τα αναφερόμενα τοπωνύμια, αποσαφηνίζονται ή ερμηνεύονται ποικίλα στοιχεία και πληροφορίες του κειμένου. Τέλος, εκτός από τους πίνακες αξιομνημόνευτων λέξεων και κυρίων ονομάτων, παρατίθενται index Graecitatis και index troporum et figurarum.
Prospects for the Development of Crisis Phenomena in the Economies of Developed Countries
Authors: Basovskaya Elena , Basovskiy Leonid
Published: August 2023

The paper provides a forecast for the development of crisis phenomena in the economies of developed countries based on the modeling of N. Kondratiev’s cycles in the time series of real per capita GDP. To determine the dates of the beginning of the upward half-waves of the Kondratiev’s cycles, econometric models with a cyclic (harmonic) component were built. As a result of the study, it was found that the earliest manifestations of growth instability, the possibility of crisis phenomena in the economy are typical for the USA, Great Britain, and Italy. For most developed countries, the 2020s are the most likely opportunities for the development of crisis phenomena. Taking into account the possible reduction in the duration of Kondratiev’s cycles in post-industrial economic systems, a spectral analysis of quotations on the US stock market was performed, which showed a reduction in the duration of cycles to 40 years. The results obtained allow us to give the following estimate. For most developed countries, the most likely opportunities for the development of crisis phenomena are the 2010s and 2020s. Systemic crises in the economies of most developed countries can be expected in the 2020s and 2030s.
Methodology for Choosing an Organization's Development Strategy Based on the Composition of a Polygon of Its Factors on a Swot Field
Authors: Polyakov V. , Fomicheva I. , Yudina O.
Published: August 2023

An example of the choice of strategies based on the data of the expert matrix of SWOT analysis is considered. The vectors of the strategy field selection are shown. To coordinate expert assessments, the method of experts’ competence coefficients was adopted. A methodology for choosing an organization’s development strategy based on SWOT analysis data is proposed. Variants of strategies are proposed depending on the position of the matrix field.
Methods of conducting classes with preschool children using sports games
Authors: Bohdanovskyj I. , Konoh A.
Published: August 2023

The article reveals the role of sports games in the development of physical qualities of older preschool children. The conducted research made it possible to establish the interdependence between learning movements from sports games and the development of physical qualities of the specified category of children. It was concluded that the method of conducting classes among preschool children is important, and the use of a systematic approach to the formation of movement techniques during sports games (badminton, football, basketball, volleyball, table tennis, floorball) forms the basis for the development of certain physical qualities.
OS RETIRANTES DE PORTINARI Uma Estética da Miséria, da Fome e da Morte
Authors: Ferreira Gilmar Leite
Published: August 2023

O presente artigo intitulado Os Retirantes de Portinari: uma estética da miséria, da fome e da morte é uma intepretação fundamentada na filosofia de Merleau-Ponty, na literatura e na educação, tendo como método a descrição fenomenológica. O objetivo é a experiência sensível como uma educação do olhar sobre a obra de arte. Nesse sentido, convido o leitor, por meio da linguagem sensível, para entrar através da escrita em alguns quadros de Portinari e perceber o êxodo, a miséria, a fome e a morte, revelando a estética assustadora dos corpos esquálidos dos sertanejos. Através de uma escrita poética e interdisciplinar, narro à jornada do desespero na extrema metafísica dos corpos expressivos dos sertanejos, nos quais, uma ontologia da vida revela-se na tragédia da fome, diante da ameaça da morte.  Nessa perspectiva, o sofrimento e a morte são transubstanciados nas cores e nos desenhos dos quadros do Portinari. Como resultado, o compreendo as causas do êxodo, não é apenas por questões climáticas, mas a opressão do latifúndio e o descaso dos governos, nos séculos passados.
Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports
Authors: Khedr Anwar , Hennawi Hussam Al , Khan Muhammed Khuzzaim , Eissa Aalaa , Mir Mikael , Rauf Ibtisam , Nitesh Jain , Surani Salim , Khan Syed Anjum
Published: August 2023

Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.