bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjuring carbon: Resource materialities in Timor-Leste
Authors: Palmer Lisa , Jackson Sue
Published: January 2023

In this paper, we trace the social and material effects of a carbon verification encounter in Timor-Leste. Foregrounding the relational historicity of these resource materialities, we inquire into the disorientating but potentially generative place-based effects of carbon offsetting. We unpack carbon's elusive and unruly materiality through our participation in a verification event connected to a reforestation and carbon-offsetting program that encourages individuals and organisations from Australia to compensate for their greenhouse gas emissions by purchasing carbon credits from subsistence farmers in Timor-Leste. We interpret this making, or conjuring, of carbon through interactions between technical experts, program managers, staff, and participants over a 4-day audit of the program and, with the benefit of subsequent interviews with farmers, examine how the opacity of the carbon credit's materiality and its measurement leads to community scepticism and demands for greater methodological clarity and oversight. At the same time, we take issue with critics of market-based conservation programs who assert that carbon offsetting leads inevitably to severe adverse impacts for local communities. Activating a generative understanding of the economic logics of ‘commodity indigenisation’ through attention to the ‘cultural biographies’ or life cycle of things, we evidence fluid movements: complex socio-natural relations and moral economies that humanise nature to reveal and potentially reconfigure the otherwise alienating effects of carbon commodities and their socio-natural technical complex.
Introduction to a review series on banked allogeneic immune effector cells
Authors: Heslop Helen E.
Published: January 2023

Complex patient-specific manufacturing and variable potency due to poor T-cell fitness limit advances in autologous chimeric antigen receptor T therapies and support the potential attractiveness of having potent immune effector cell therapy that is readily available “off the shelf.” Edited by Associate Editor Helen Heslop and authored by leading experts, this review series focuses on several types of banked allogeneic immune cell therapies under development, highlighting their attributes and speculating on their anticipated future place in the therapeutic armamentarium.
Effects of dietary variation on lignocellulose degradation and physiological properties of Nicobium hirtum larvae
Authors: Krishanti Ni Putu Ratna Ayu , Tobimatsu Yuki , Afifi Osama Ahmed , Tarmadi Didi , Himmi Setiawan Khoirul , Umezawa Toshiaki , Ohmura Wakako , Yoshimura Tsuyoshi
Published: January 2023

We investigated the feeding behavior of larvae of the wood-destroying beetle Nicobium hirtum (Coleoptera: Anobiidae), an important wood pest in Japan, to determine the effects of dietary variation on lignocellulose degradation and larval growth and survival. Cultured colonies of N. hirtum larvae were fed artificial diets containing various amounts of starch (20, 50, and 80 wt%) mixed with hardwood (Shorea) lignocellulose. The polysaccharide degradation by N. hirtum was determined by chemical analyses of the initial artificial diets and fecal residues collected during the feeding experiment. Starch was preferentially decomposed when the larvae were fed the high-starch diet, whereas the decompositions of cellulose and hemicelluloses were more prominent when the larvae were fed medium- or low-starch diets. The larvae’s size and survival were recorded periodically to determine the diets’ effects on larval development. The survival rates ranged from 60 to 87% and were highest for the larvae fed the medium-starch diet and lowest for those fed the high-starch diet. Body size was highest in the larvae fed the high-starch diet. Fecal size increased along with the larval size increase. Overall, these results suggest that although starch is an essential carbon source for N. hirtum larval growth, lignocellulose also plays a key role as a nutrient that maintains the physiological activities of N. hirtum larvae and enhances their survival.
Investigation on the mechanisms of human sperm DNA damage based on the proteomics analysis by SWATH-MS
Authors: Zhu Chun-Hui , Wei Ye , Chen Fang , Li Feng , Zhang Sheng-Min , Dong Nai-Jun , Xue Tong-Min , Liu Kai-Feng , Cui Heng-Mi , Lu Jin-Chun
Published: January 2023

Background

Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF.

Methods

Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis.

Results

A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis.

Conclusions

Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage.
Distribution, health risk assessment, and water quality criteria of phthalate esters in Poyang Lake, China
Authors: Ai Shunhao , Wang Xiaonan , Gao Xiangyun , Xu Qianyun , Li Ji , Liu Zhengtao
Published: January 2023

Although China has been the main manufacturer and consumer of phthalate esters (PAEs), human health ambient water quality criteria (AWQCs) have not been proposed for these chemicals. In this study, the distribution and bioaccumulation of six PAEs (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), butyl benzyl phthalate (BBP), bis (2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP)) were investigated in 11 edible fish species collected from Poyang Lake, China. The results showed that the total concentrations of the six PAEs in the fish ranged between 118.63 and 819.84 μg/kg wet weight (mean of 327.50 ± 190.44 μg/kg). DMP, DEP, DBP, and DEHP were detected in all samples, of which DEHP and DBP were two of the most predominant phthalates, accounting for more than 90% of the total PAEs. The DEHP concentrations in fish with different habitat preferences were different, demersal species were significantly higher than pelagic species (p < 0.05). The mean natural logarithmic bioaccumulation factors (log BAFs) of PAEs increased with increasing lipophilicity of the substances, which yielded the following regression equation: log BAF (L/kg) = 0.103 log Kow + 2.158 (r2 = 0.940, p < 0.05, n = 4). Using this quantitative structure–activity relationship to calculate BAFs for the remaining undetected substances (BBP and DnOP) to derive AWQCs. According to the natural parameters, the human health AWQCs relating to PAE concentrations for water and fish consumption were derived as 9.4 × 103 (DMP), 5.0 × 102 (DEP), 4.2 × 101 (DBP), 1.1 (BBP), 8.6 × 10− 2 (DEHP), and 2.0 (DnOP) μg/L. Human health risk assessment indicated that the dietary intake of DEHP may exert a carcinogenic effect on residents of the Poyang Lake region. The results provide important input to assess the health risk posed by PAEs contaminated surface water.
The dynamics of wage dispersion between firms: the role of firm entry and exit
Authors: Schröpf Benedikt
Published: January 2023

Although wage inequality is an important and widely studied issue, the literature is vastly silent on the relationship between firm entry and exit and the wage dispersion between firms. Using a 50% random administrative sample of West German establishments over the period 1976–2017, I study wage dispersion dynamics between and within the groups of entering, exiting, and incumbent establishments by examining the distribution of average wages across establishments. The results show that entering establishments became increasingly unequal over time, thereby contributing to the rise in wage dispersion between establishments. However, exit rates of young and low-wage establishments have dampened this effect. These findings suggest considering the consequences for wage inequality when designing and assessing policy instruments for firm entry and exit.
Cognitive function in older patients and their stress challenge using different anesthesia regimes: a single center observational study
Authors: Wagner Soeren , Breitkopf Martin , Ahrens Elena , Ma Haobo , Kuester Olivia , Thomas Christine , von Arnim Christine A. F. , Walther Andreas
Published: January 2023

Background

With increasing age older patients are at higher risk for cognitive decline after surgery. Even tailored anesthesia procedures in older patients remain a high risk for postoperative cognitive disorder. Additional stress derived from anxiety and anesthesia itself can negatively impact postoperative cognitive outcomes. The objective of this study was to evaluate the impact of general versus regional anesthesia on postoperative cognitive disorder and indicators of perioperative stress in elderly undergoing surgery.

Methods

In this single center prospective study between December 2014 and November 2015, 46 patients aged 50 to 85 years undergoing dermatology surgery were enrolled. Patients were stratified by receiving general versus regional nerve anesthesia. On three consecutive days, saliva cortisol levels were analyzed three times per day. Cognitive function was assessed on the day before and the day after surgery using comprehensive neuropsychological testing of multiple cognitive functions including memory, executive function, attention and processing speed.

Results

Comparing the regional anesthesia group (RAG, n = 28) with the general anesthesia group (GAG, n = 18) no significant difference in the postoperative cognitive function was observed. However, patients in the GAG had significantly higher postoperative cortisol levels when compared to patients in the RAG. In both groups, a peak of cortisol value was detected on the day of surgery, which was higher in the GAG in comparison to the RAG.

Conclusions

We did not observe a difference in postoperative cognitive function between patients undergoing regional or general anesthesia for dermatology surgery. However, we found lower cortisol level in the RAG. Based on these findings, future studies should investigate alternatives to reduce stress in a general anesthesia setting.

Trial registration

ClinicalTrials.gov ID: NCT02505815.
How do individual, social, environmental, and resilience factors shape self-reported health among community-dwelling older adults: a qualitative case study
Authors: Whitmore Carly , Markle-Reid Maureen , McAiney Carrie , Fisher Kathryn , Ploeg Jenny
Published: January 2023

Background

While older adults are living longer, they often face health challenges, including living with multiple chronic conditions. How older adults respond and adapt to the challenges of multimorbidity to maintain health and wellness is of increasing research interest. Self-reported health, emerging as an important measure of health status, has broad clinical and research applications, and has been described as a predictor of future morbidity and mortality. However, there is limited understanding of how individual, social, and environmental factors, including those related to multimorbidity resilience, influence self-reported health among community-dwelling older adults (≥ 65 years).

Methods

Informed by the Lifecourse Model of Multimorbidity Resilience, this explanatory case study research explored older adults’ perceptions of how these factors influence self-reported health. Data were generated through semi-structured telephone interviews with community-dwelling older adults.

Results

Fifteen older adults participated in this study. Four key themes, specific to how these older adults describe individual, social, environmental, and multimorbidity resilience factors as shaping their self-reported health, were identified: 1) health is a responsibility – “What I have to do”; 2) health is doing what you want to do despite health-related limitations – “I do what I want to do”; 3) the application and activation of personal strengths – “The way you think”, and; 4) through comparison and learning from others – “Looking around at other people”. These themes, while distinct, were found to be highly interconnected with recurring concepts such as independence, control, and psychological health and well-being, demonstrating the nuance and complexity of self-reported health.

Conclusions

Findings from this study advance understanding of the factors that influence assessments of health among community-dwelling older adults. Self-reported health remains a highly predictive measure of future morbidity and mortality in this population, however, there is a need for future research to contribute additional understanding in order to shape policy and practice.
Effects of contact tracing and nucleic acid testing on the COVID-19 outbreak in Zunyi, China: data-driven study using a branching process model
Authors: Feng Jun , Zhu Wenlong , Ye Xingui , Liu Zhixi , Zhu Yue , Wu Qinyi , Yang Guanghong , Wang Weibing
Published: January 2023

Background

During October 2021, China experienced localized outbreaks of COVID-19 in many cities. We analyzed the small local outbreak in Zunyi (Guizhou Province), a major city in southwestern China, and modeled the effects of different interventions on this outbreak.

Methods

Data on infections and contacts, provided by the Health Commission of Guizhou Province, were used to analyze the epidemiological characteristics of the outbreak and calculate the effectiveness of vaccination. A branching process model was used to simulate the outbreak. This model considered the time interval from exposure of the initial case to confirmation, the number of potential infections caused by the initial case, and the effects of the different interventions.

Results

From 18 to 25 October 2021, there were 12 patients with COVID-19 in Zunyi. Overall, the average age was 67.17 years-old, 8 patients were females, and 1 patient had an asymptomatic infection. The effectiveness of two-dose inactivated vaccine against SARS-CoV-2 infection was 16.7% (95% CI: 2.8% to 99.7%). The initial case was infected on 11 or 12 October 2021, 6.40 (95% CI: 6.37, 6.42; IQR: 4.92, 7.63) days before confirmation while the travelling in Lanzhou (Gansu Province). There were 10.07 (95% CI: 10.04, 10.09; IQR: 7.86, 11.93) potential secondary cases. When the effective vaccine coverage reached 60%, the probability of cumulative cases exceeding 20 was less than 8.77%, even if contact tracing was relaxed or eliminated. However, if the probability of tracing contacts decreased, earlier initiation of nucleic acid testing was necessary to control the outbreak.

Conclusions

The COVID-19 outbreak in Zunyi was controlled quickly due to moderately effective vaccine coverage and rapid contact tracing. For controlling localized outbreaks, vaccination and contact tracing seemed to be more effective than massive nucleic acid testing in the initial phase of transmission. However, if there is low effective vaccine coverage or insufficient contact tracing, nucleic acid testing should start earlier.
Temporal discrepancies in “rapid” HIV testing: explaining misdiagnoses at the point-of-care in Zimbabwe
Authors: Skovdal Morten , Jensen Frederik Jacob Brainin , Maswera Rufurwokuda , Beckmann Nadine , Nyamukapa Constance , Gregson Simon
Published: January 2023

Background

Rapid diagnostic tests have revolutionized the HIV response in low resource and high HIV prevalence settings. However, disconcerting levels of misdiagnosis at the point-of-care call for research into their root causes. As rapid HIV tests are technologies that cross borders and have inscribed within them assumptions about the context of implementation, we set out to explore the (mis)match between intended and actual HIV testing practices in Zimbabwe.

Methods

We examined actual HIV testing practices through participant observations in four health facilities and interviews with 28 rapid HIV testers. As time was identified as a key sphere of influence in thematic analyses of the qualitative data, a further layer of analysis juxtaposed intended (as scripted in operating procedures) and actual HIV testing practices from a temporal perspective.

Results

We uncover substantial discrepancies between the temporal flows assumed and inscribed into rapid HIV test kits (their intended use) and those presented by the high frequency testing and low resource and staffing realities of healthcare settings in Zimbabwe. Aside from pointing to temporal root causes of misdiagnosis, such as the premature reading of test results, our findings indicate that the rapidity of rapid diagnostic technologies is contingent on a slow, steady, and controlled environment. This not only adds a different dimension to the meaning of “rapid” HIV testing, but suggests that errors are embedded in the design of the diagnostic tests and testing strategies from the outset, by inscribing unrealistic assumptions about the context within which they used.

Conclusion

Temporal analyses can usefully uncover difficulties in attuning rapid diagnostic test technologies to local contexts. Such insight can help explain potential misdiagnosis ‘crisis points’ in point-of-care testing, and the need for public health initiatives to identify and challenge the underlying temporal root causes of misdiagnosis.
Sonographic prediction of intraductal papillary carcinoma with partially cystic breast lesions
Authors: Gao Luying , Lai Xingjian , Zhang Jing , Jiang Yuxin , Li Jianchu
Published: January 2023

Background

Intraductal papillary carcinoma (IDPC) is a rare but fatal disease. Preoperative ultrasound diagnosis of IDPC remains challenging and meaningful. The aim of the study was to determine an effective ultrasound model to predict intraductal papillary carcinoma (IDPC) in patients with partially cystic breast lesions on ultrasound.

Methods

We reviewed female patients with breast nodules who underwent biopsy or surgery between 2004 and 2019, and pathological results were used as the reference standard. We finally included 21 IDPC patients with partially cystic lesions on preoperative ultrasound matched to 40 patients with intraductal papilloma. The association of ultrasound features with IDPC was analysed.

Results

Posterior echo enhancement (P < 0.001), tumour size (P = 0.002), irregular shape (P = 0.003), wide base (P = 0.003), solid-mainly component (P = 0.013), rich Doppler flow (P < 0.001) and multiple lesions (P = 0.044) were associated with IDPC by univariate analysis. Based on univariate analysis, variables were included in the regression analysis to obtain independent factors. The regression analysis showed that microcalcification, multiple lesions, posterior echo enhancement, wide base of solid components and rich colour Doppler flow were predictors for IDPC (P < 0.001). The collective model of the independent factors (microcalcification, multiple lesions, posterior echo enhancement, wide base of solid components and rich colour Doppler flow) could predict IDPC with an area under the curve (AUC) of 0.99 (95% CI 0.95–1.00). The collective model had a better net benefit demonstrated by the decision curve.

Conclusion

Ultrasonic features may be an applicable model for predicting IDPC with partially cystic breast lesions on ultrasound and has a better potential to facilitate decision-making preoperatively.
Short-term impact of COVID-19 pandemic on low back pain: data from the PAMPA Cohort, Brazil
Authors: Caputo Eduardo L. , Ferreira Paulo H. , Feter Natan , Doring Igor R. , Leite Jayne S. , Alt Ricardo , Cassuriaga Júlia , Reichert Felipe F. , Rombaldi Airton J. , da Silva Marcelo C.
Published: January 2023

Background

To evaluate the short-term impact of COVID-19 pandemic on low back pain (LBP) outcomes in southern Brazil.

Methods

Data from the PAMPA Cohort were analyzed. Adults were recruited between June and July 2020 in the Rio Grande do Sul state using online-based strategies. Participants responded a self-reported, online questionnaire on LBP with two timepoints: before (retrospectively) and during COVID-19 pandemic. We assessed LBP experience, LBP-related activity limitation (no/yes), and LBP intensity (0 to 10 [strongest pain]).

Results

From a total sample of 2,321 respondents (mean age: 37.6 ± 13.5; 75.4% women), the prevalence of LBP did not change significantly from before (74.7% [95%CI 72.3; 76.9]) to the first months of pandemic (74.2% [95%CI 71.9; 76.3]). However, an increased pain levels (β: 0.40; 95%CI 0.22; 0.58) and a higher likelihood for activity limitation due to LBP was observed (PR 1.14; 95%CI 1.01; 1.29). Longitudinal analyzes showed that age, gender, BMI, chronic diseases, physical activity, and anxiety and depression symptoms, were associated with LBP in the first pandemic months.

Conclusion

Although the prevalence of LBP did not change at the first months of COVID-19 pandemic, LBP-induced impairment in daily activities and pain intensity was higher when compared to before the pandemic.
Impact of ambient air pollution exposure during pregnancy on adverse birth outcomes: generalized structural equation modeling approach
Authors: Mitku Aweke A. , Zewotir Temesgen , North Delia , Jeena Prakash , Asharam Kareshma , Muttoo Sheena , Tularam Hasheel , Naidoo Rajen N.
Published: January 2023

Background

Air pollution and several prenatal factors, such as socio-demographic, behavioural, physical activity and clinical factors influence adverse birth outcomes. The study aimed to investigate the impact of ambient air pollution exposure during pregnancy adjusting prenatal risk factors on adverse birth outcomes among pregnant women in MACE birth cohort.

Methods

Data for the study was obtained from the Mother and Child in the Environment (MACE) birth cohort study in Durban, South Africa from 2013 to 2017. Land use regression models were used to determine household level prenatal exposure to PM2.5, SO2and NOx. Six hundred and fifty-six births of pregnant females were selected from public sector antenatal clinics in low socio-economic neighbourhoods. We employed a Generalised Structural Equation Model with a complementary log–log-link specification.

Results

After adjustment for potential prenatal factors, the results indicated that exposure to PM2.5was found to have both significant direct and indirect effects on the risk of all adverse birth outcomes. Similarly, an increased level of maternal exposure to SO2during pregnancy was associated with an increased probability of being small for gestational age. Moreover, preterm birth act a mediating role in the relationship of exposure to PM2.5, and SO2with low birthweight and SGA.

Conclusions

Prenatal exposure to PM2.5and SO2pollution adversely affected birth outcomes after controlling for other prenatal risk factors. This suggests that local government officials have a responsibility for better control of air pollution and health care providers need to advise pregnant females about the risks of air pollution during pregnancy.
Activity-to-sedentary ratio provides novel insight into mortality reduction among male survivors of cardiovascular disease in the United States: national health and nutrition examination survey, 2007–2014
Authors: Ding Yuanyuan , Chen Jiahao , Niu Mengying , Xiao Qi , Zhao Hongqin , Pan Xudong , Zhu Xiaoyan
Published: January 2023

Background

Lower physical activity and sedentary behavior have been identified as modifiable risk factors for cardiovascular disease (CVD). However, the quantitative, dose-response association between activity-to-sedentary ratio (ASR) and mortality is unknown.

Methods

Prospective cohort studies with participants 50 to 80 years that reported the association between recreational physical activity, sedentary behavior, and all-cause mortality were included from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) and followed through December 31, 2015. Cox or Weibull regression models and restricted cubic splines were used to determine the association between ASR and all-cause mortality.

Results

Sixty deaths occurred among 498 CVD survivors, with a median of 56 months of follow-up. After accounting for all covariates, CVD survivors with an ASR between 0.21 and 0.57 (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25–0.87) and those with an ASR more than 0.57 (HR, 0.40; 95% CI, 0.20–0.81) were at significantly lower risk for mortality than participants with an ASR <  0.21. Moreover, a nonlinear negative association and an L-shaped association were observed for the level of ASR with risk of mortality among CVD survivors (P for nonlinearity = 0.004). What’s more, adjusting for covariates, a statistically significant interaction (P for interaction = 0.016) between sex and ASR, an increase of ASR more than and equal to 0.18 was associated with a lower risk of mortality among males (HR, 0.23; 95% CI, 0.12–0.46).

Conclusions

An negative correlation between ASR and mortality in CVD survivors, especially in males when ASR is more than 0.18. Our novel findings provide further insights into easing the global burden of deaths.
Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women
Authors: Emamgholipour Solaleh , Esmaeili Fataneh , Shabani Maryam , Hasanpour Seyedeh Zahra , Pilehvari Mahsa , Zabihi-Mahmoudabadi Hossein , Motevasseli Meysam , Shanaki Mehrnoosh
Published: January 2023

Background

Animal model studies suggest that change in the members of the suppressor of the cytokine signaling (SOCS) family (mainly SOCS1 and SOCS3) is linked to the pathogenesis of obesity-related metabolic disorders. Moreover, epigenetic modification is involved in the transcriptional regulation of the SOCS gene family. Here, we aimed to evaluate the mRNA expression as well as gene promoter methylation of SOCS1 and SOCS3 in subcutaneous adipose tissue (SAT) from obese women compared to normal-weight subjects. We also intend to identify the possible association of SOCS1 and SOCS3 transcript levels with metabolic parameters in the context of obesity.

Methods

This study was conducted on women with obesity (n = 24) [body mass index (BMI) ≥ 30 kg/m 2] and women with normal-weight (n = 22) (BMI < 25 kg/m 2). Transcript levels of SOCS1 and SOCS3 were evaluated by real-time PCR in SAT from all participants. After bisulfite treatment of DNA, methylation-specific PCR was used to assess the putative methylation of 10 CpG sites in the promoter of SOCS1 and 13 CpG sites in SOCS3 in SAT from women with obesity and normal weight.

Results

It was found that unlike SOCS3, which disclosed an elevating expression pattern, the expression level of SOCS1 was lower in the women with obesity as compared with their non‐obese counterparts (P-value = 0.03 for SOCS1 transcript level and P-value = 0.011 for SOCS3 transcript level). As for the analysis of promoter methylation, it was found that SOCS1 and SOCS3 methylation were not significantly different between the individuals with obesity and normal weight (P-value = 0.45 and P-value = 0.89). Correlation analysis indicated that the transcript level of SOCS1 mRNA expression had an inverse correlation with BMI, hs-CRP levels, HOMA-IR, and insulin levels. However, the SOCS3 transcript level showed a positive correlation with BMI, waist-to-height ratio, waist circumference, hip circumference, hs-CRP, HOMA-IR, insulin, fasting blood glucose, and total cholesterol. Interestingly, HOMA-IR is the predictor of the transcript level of SOCS1 (β =  − 0.448, P-value = 0.003) and SOCS3 (β = 0.465, P-value = 0.002) in SAT of all participants.

Conclusions

Our findings point to alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues from women with obesity. Moreover, mRNA expression of SOCS1 and SOCS3 in SAT was associated with known obesity indices, insulin resistance, and hs-CRP, suggesting the contribution of SOCS1 and SOCS3 in the pathogenesis of obesity-related metabolic abnormalities. However, further studies are required to establish this concept.
Clinical practice guideline adaptation for risk-based caries management in 18–55 year-old Iranian adults
Authors: Pakdaman A. , Gholizadeh N. , Kharazifard M. J. , Eshrati M.
Published: January 2023

Purpose

To adapt an evidence-based clinical practice guideline (CPG) for risk-based management of caries in 18–55 year-old Iranian adults.

Methods

A multidisciplinary adaptation team reviewed evidence-based guidelines such as the NICE, SIGN, and ADA according to the defined clinical questions. In addition, databases such as the PubMed and Google Scholar were searched and CPGs were screened and appraised using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) tool. Clinical scenarios were developed and their level of evidence, clinical advantage and adaptability were assessed. Following a two-round ranking by experts, the final recommendations were selected using the RAND-UCLA appropriateness method.

Results

Of 17 CPGs, 5 were selected as the source guidelines for adaptation. To assess the risk of caries in the adult population, reduced Cariogram (without saliva tests) and CAMBRA were suggested as diagnostic tools. In addition, 53 risk-based recommendations on the preventive care (including the use of fluoride toothpaste, fluoride, and chlorhexidine mouthwash, at home and in-office fluoride gel, fluoride varnish, mouth buffering, and sealant), operative intervention threshold, and follow-up interval were adapted for Iranian adults.

Conclusions

A guideline was adapted for risk-based management of dental caries in Iranian adults. This helps local dentists in decision making and promoting oral health of adults. Further research is needed to assess the external validity and feasibility of the adapted guideline in the Iranian population.
High porosity 3D printed titanium mesh allows better bone regeneration
Authors: Ma Rui , Liu Qian , Zhou Libo , Wang Lingxiao
Published: January 2023

Background

Most patients with insufficient bone mass suffer from severe horizontal or vertical bone defects in oral implant surgery. The purpose of this study was to compare the bone regeneration effects of titanium meshes with different porosity in the treatment of bone defects.

Methods

Nine beagle dogs were equally divided into three groups based on execution time. Three months after the extraction of the first to fourth premolars of the mandible, three bone defects were randomly made in the mandible. Bone particles and three kinds of three-dimensional (3D) printed titanium nets with different porosities (low porosity group (LP), 55%; medium porosity group (MP), 62%; and high porosity group (HP), 68%) were replanted in situ. The beagles were killed 4, 8, and 12 weeks after surgery. Formalin-fixed specimens were embedded in acrylic resin. The specimens were stained with micro-CT, basic fuchsin staining, and toluidine blue staining.

Results

Micro-CT analysis showed that the trabecular thickness, trabecular number, and bone volume fraction of the HP group were higher than those of the other two groups. Moreover, the trabecular separation of the HP group decreased slightly and was lower than that of the MP and LP groups. Histological staining analysis showed that the trabecular number in the HP group was higher than in the other two groups at 8 and 12 weeks, and the bone volume fraction of the HP was higher than that in the other two groups at 12 weeks. Moreover, the trabecular thickness of the MP was higher than that of the LP group at 12 weeks and the trabecular separation was lower in the HP group at 4 and 8 weeks. The differences were statistically significant (p < 0.05).

Conclusion

A 3D printed titanium mesh with HP in a certain range may have more advantages than a titanium mesh with LP in repairing large bone defects.
Predicting decompression surgery by applying multimodal deep learning to patients’ structured and unstructured health data
Authors: Jujjavarapu Chethan , Suri Pradeep , Pejaver Vikas , Friedly Janna , Gold Laura S. , Meier Eric , Cohen Trevor , Mooney Sean D. , Heagerty Patrick J. , Jarvik Jeffrey G.
Published: January 2023

Background

Low back pain (LBP) is a common condition made up of a variety of anatomic and clinical subtypes. Lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) are two subtypes highly associated with LBP. Patients with LDH/LSS are often started with non-surgical treatments and if those are not effective then go on to have decompression surgery. However, recommendation of surgery is complicated as the outcome may depend on the patient’s health characteristics. We developed a deep learning (DL) model to predict decompression surgery for patients with LDH/LSS.

Materials and method

We used datasets of 8387 and 8620 patients from a prospective study that collected data from four healthcare systems to predict early (within 2 months) and late surgery (within 12 months after a 2 month gap), respectively. We developed a DL model to use patients’ demographics, diagnosis and procedure codes, drug names, and diagnostic imaging reports to predict surgery. For each prediction task, we evaluated the model’s performance using classical and generalizability evaluation. For classical evaluation, we split the data into training (80%) and testing (20%). For generalizability evaluation, we split the data based on the healthcare system. We used the area under the curve (AUC) to assess performance for each evaluation. We compared results to a benchmark model (i.e. LASSO logistic regression).

Results

For classical performance, the DL model outperformed the benchmark model for early surgery with an AUC of 0.725 compared to 0.597. For late surgery, the DL model outperformed the benchmark model with an AUC of 0.655 compared to 0.635. For generalizability performance, the DL model outperformed the benchmark model for early surgery. For late surgery, the benchmark model outperformed the DL model.

Conclusions

For early surgery, the DL model was preferred for classical and generalizability evaluation. However, for late surgery, the benchmark and DL model had comparable performance. Depending on the prediction task, the balance of performance may shift between DL and a conventional ML method. As a result, thorough assessment is needed to quantify the value of DL, a relatively computationally expensive, time-consuming and less interpretable method.
Applying value-based strategies to accelerate access to novel cancer medications: guidance from the Oncology Health Economics Expert Panel in Qatar (Q-OHEP)
Authors: Hamad Anas , Elazzazy Shereen , Bujassoum Salha , Rasul Kakil , Gaziev Javid , Cherif Honar , Al-Boloshi Zakiya , Hanssens Yolande , Saleh Ayman , Rasheed Hadi Abu , Al-Badriyeh Daoud , Babiker Ahmed , Hmaidan Amid Abu , Al-Hail Moza
Published: January 2023

Background

In line with global trends, cancer incidence and mortality may have decreased for specific types of cancer in Qatar. However, the cancer-related burden on patients, healthcare systems, and the economy is expected to expand; thus, cancer remains a significant public healthcare issue in Qatar. Qatar’s free access to cancer care represents a considerable economic burden. Ensuring the best utilization of financial resources in the healthcare sector is important to provide unified and fair access to cancer care for all patients. Experts from the Qatar Oncology Health Economics Expert Panel (Q-OHEP) aimed to establish a consistent and robust base for evaluating oncology/hematology medications; involve patients’ insights to accelerate access to cutting-edge medications; increase the value of cancer care; and reach a consensus for using cost-effective strategies and efficient methodologies in cancer treatment.

Methods

The Q-OHEP convened on 30 November 2021 for a 3-hour meeting to discuss cancer management, therapeutics, and health economics in Qatar, focusing on four domains: (1) regulatory, (2) procurement, (3) treatment, and (4) patients. Discussions, guided by a moderator, focused on a list of suggested open-ended questions.

Results

Some of the salient recommendations included the development of a formal, fast-track, preliminary approval pathway for drugs needed by patients with severe disease or in critical condition; and encouraging and promoting the conduct of local clinical trials and real-world observational studies using existing registry data. The Q-OHEP also recommended implementing a forecast system using treatment center data based on the supply/demand of formulary oncology drugs to detect treatment patterns, estimate needs, expedite procurement, and prevent shortages/delays. Furthermore, the panel discussed the needs to define value concerning cancer treatment in Qatar, implement value-based models for reimbursement decision-making such as health technology assessment and multiple-criteria decision analysis, and promote patient education and involvement/feedback in developing and implementing cancer management guidelines.

Conclusion

Herein, we summarize the first Q-OHEP consensus recommendations, which aim to provide a solid basis for evaluating, registering, and approving new cancer medications to accelerate patient access to novel cancer treatments in Qatar; promote/facilitate the adoption and collection of patient-reported outcomes; and implement value-based cancer care in Qatar.
Nonribosomal antibacterial peptides isolated from Streptomyces agglomeratus 5-1-3 in the Qinghai-Tibet Plateau
Authors: Jiang Kan , Chen Ximing , Zhang Wei , Guo Yehong , Liu Guangxiu
Published: January 2023

Background

New antibiotics are urgently needed in clinical treatment of superdrug-resistant bacteria. Nonribosomal peptides (NRPs) are a major source of antibiotics because they exhibit structural diversity, and unique antibacterial mechanisms and resistance. Analysis of gene clusters of S. agglomeratus 5-1-3 showed that Clusters 3, 6, 12, 21, and 28 were used to synthesize NRPs. Here, we examined secondary metabolites of S. agglomeratus 5-1-3 isolated from soils in the Qinghai-Tibet Plateau, China, for NRPs with antibacterial activity.

Results

We isolated a total of 36 Streptomyces strains with distinct colony morphological characteristics from 7 soil samples. We screened 8 Streptomyces strains resistant to methicillin-resistant Staphylococcus aureus (MRSA). We then selected S. agglomeratus 5-1-3 for further study based on results of an antibacterial activity test. Here, we isolated three compounds from S. agglomeratus 5-1-3 and characterized their properties. The crude extract was extracted with ethyl acetate and purified with column chromatography and semipreparative high-performance liquid chromatography (HPLC). We characterized the three compounds using NMR analyses as echinomycin (1), 5,7,4ʹ-trihydroxy-3.3′,5′-trimethoxy flavone (2), and 2,6,2′, 6′-tetramethoxy-4,4-bis(2,3-epoxy-1-hydroxypropyl)-biphenyl (3). We tested the antibacterial activity of pure compounds from strain 5-1-3 with the Oxford cup method. NRP echinomycin (1) showed excellent anti-MRSA activity with a minimum inhibitory concentration (MIC) of 2.0 μg/mL. Meanwhile, MIC of compound 2 and 3 was 128.0 μg/mL for both. In addition, 203 mg of echinomycin was isolated from 10 L of the crude extract broth of strain 5-1-3.

Conclusion

In this study, S. agglomeratus 5-1-3 with strong resistance to MRSA was isolated from the soils in the Qinghai-Tibet Plateau. Strain 5-1-3 had a high yield of echinomycin (1) an NRP with a MIC of 2 μg/mL against MRSA. We propose that echinomycin derived from S. agglomeratus 5-1-3 may be a potent antibacterial agent for pharmaceutical use.
Treatment escalation patterns to start biologics in refractory moderate juvenile dermatomyositis among members of the Childhood Arthritis and Rheumatology Research Alliance
Authors: Sherman Matthew A. , Kim Hanna , Banschbach Katelyn , Brown Amanda , Gewanter Harry L. , Lang Bianca , Perron Megan , Robinson Angela Byun , Spitznagle Jacob , Stingl Cory , Syverson Grant , Tory Heather O. , Spencer Charles H. , Tarvin Stacey E.
Published: January 2023

Background

Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking.

Methods

The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher’s exact test was used to compare the distribution of responses to each survey question.

Results

One hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1–2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience.

Conclusion

Most respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices.
Protein kinase B (AKT) upregulation and Thy-1-αvβ3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis
Authors: Pérez-Núñez Ramón , Chamorro Alejandro , González María Fernanda , Contreras Pamela , Artigas Rocío , Corvalán Alejandro H. , van Zundert Brigitte , Reyes Christopher , Moya Pablo R. , Avalos Ana María , Schneider Pascal , Quest Andrew F. G. , Leyton Lisette
Published: January 2023

Background

In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvβ3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined.

Methods

Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi).

Results

The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation.

Conclusions

Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.