bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of tiered measures on social contact and mixing patterns of in Italy during the second wave of COVID-19
Authors: Tizzani Michele , De Gaetano Alessandro , Jarvis Christopher I. , Gimma Amy , Wong Kerry , Edmunds W John , Beutels Philippe , Hens Niel , Coletti Pietro , Paolotti Daniela
Published: May 2023

Background

Most countries around the world enforced non-pharmaceutical interventions against COVID-19. Italy was one of the first countries to be affected by the pandemic, imposing a hard lockdown, in the first epidemic wave. During the second wave, the country implemented progressively restrictive tiers at the regional level according to weekly epidemiological risk assessments. This paper quantifies the impact of these restrictions on contacts and on the reproduction number.

Methods

Representative (with respect to age, sex, and region of residence) longitudinal surveys of the Italian population were undertaken during the second epidemic wave. Epidemiologically relevant contact patterns were measured and compared with pre-pandemic levels and according to the level of interventions experienced by the participants. Contact matrices were used to quantify the reduction in the number of contacts by age group and contact setting. The reproduction number was estimated to evaluate the impact of restrictions on the spread of COVID-19.

Results

The comparison with the pre-pandemic baseline shows a significant decrease in the number of contacts, independently from the age group or contact settings. This decrease in the number of contacts significantly depends on the strictness of the non-pharmaceutical interventions. For all levels of strictness considered, the reduction in social mixing results in a reproduction number smaller than one. In particular, the impact of the restriction on the number of contacts decreases with the severity of the interventions.

Conclusions

The progressive restriction tiers implemented in Italy reduced the reproduction number, with stricter interventions associated with higher reductions. Readily collected contact data can inform the implementation of mitigation measures at the national level in epidemic emergencies to come.
Exploring the factors contributing to low vaccination uptake for nationally recommended routine childhood and adolescent vaccines in Kenya
Authors: Essoh Tene-Alima , Adeyanju Gbadebo Collins , Adamu Abdu A. , Tall Haoua , Aplogan Aristide , Tabu Collins
Published: May 2023

Background

Vaccination remains the most effective means of reducing the burden of infectious disease among children. It is estimated to prevent between two to three million child deaths annually. However, despite being a successful intervention, basic vaccination coverage remains below the target. About 20 million infants are either under or not fully vaccinated, most of whom are in Sub-Saharan Africa region. In Kenya, the coverage is even lower at 83% than the global average of 86%. The objective of this study is to explore the factors that contribute to low demand or vaccine hesitancy for childhood and adolescent vaccines in Kenya.

Methods

The study used qualitative research design. Key Informant Interviews (KII) was used to obtain information from national and county-level key stakeholders. In-depth Interviews (IDI) was done to collect opinions of caregivers of children 0–23 months and adolescent girls eligible for immunization, and Human papillomavirus (HPV) vaccine respectively. The data was collected at the national level and counties such as Kilifi, Turkana, Nairobi and Kitui. The data was analyzed using thematic content approach. A total of 41 national and county-level immunization officials and caregivers formed the sample.

Results

Insufficient knowledge about vaccines, vaccine supply issues, frequent healthcare worker’s industrial action, poverty, religious beliefs, inadequate vaccination campaigns, distance to vaccination centers, were identified as factors driving low demand or vaccine hesitancy against routine childhood immunization. While factors driving low uptake of the newly introduced HPV vaccine were reported to include misinformation about the vaccine, rumors that the vaccine is a form of female contraception, the suspicion that the vaccine is free and available only to girls, poor knowledge of cervical cancer and benefits of HPV vaccine.

Conclusions

Rural community sensitization on both routine childhood immunization and HPV vaccine should be key activities post COVID-19 pandemic. Likewise, the use of mainstream and social media outreaches, and vaccine champions could help reduce vaccine hesitancy. The findings are invaluable for informing design of context-specific interventions by national and county-level immunization stakeholders. Further studies on the relationship between attitude towards new vaccines and connection to vaccine hesitancy is necessary.
Relationship between spinal imbalance and knee osteoarthritis by using full-body EOS
Authors: Fu Pengfei , Xu Wu , Xu Pingcheng , Huang Jun , Guo Jiong Jiong
Published: May 2023

Background

Orthostatic state is maintained by harmonizing the spine, pelvis and lower extremities. In the past few decades, several studies have demonstrated the associations between spinal imbalance and generalized osteoarthritis. The compensatory mechanisms of pelvis translation and knee flexion, however, have not been fully assessed.

Methods

A total of 213 volunteers, over 40 years of age, were recruited. Radiological measurements were performed by EOS imaging system. Pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), global tilt (GT), hip-knee-angle (HKA), knee flexion angle (KFA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. On the basis of SRS-Schwab, the subjects were classified into decompensated group (PI-LL > 20°), compensated group(10° ≤ PI-LL ≤ 20°), and normal group (PI-LL < 10°). Differences in radiographic parameters among groups were evaluated. Data of Knee Society Score (KSS) and Oswestry Disability Index (ODI) score were collected via questionnaires.

Results

Decompensated group showed larger pelvic parameters (PT) and low extremity parameters (LDFA, MPTA, HKA and KFA) than normal group (P < 0.05). Pelvic parameter was larger in the compensated group (median = 31°) compared to the normal group (median = 17°) (P < 0.05). There was no difference in low extremity parameters between the compensated and normal groups. At the sagittal plane, the radiological parameters of spine were greater in subjects with patellofemoral joint pain (PFP) than without PFP (P = 0.058). Higher PI-LL values were observed in women (P < 0.05).

Conclusions

A correlation between sagittal spinal imbalance and knee joint angles was recognized. The progression of knee and low back pain was associated with the severity of sagittal spinal imbalance. Pelvic retroversion was considered to be the probable compensatory mechanism.
Transparency of clinical practice guideline funding: a cross-sectional analysis of the German AWMF registry
Authors: Napierala Hendrik , Schuster Angela , Gehrke-Beck Sabine , Heintze Christoph
Published: May 2023

Background

While reporting of individual conflicts of interest is formalised, it is unclear to what extent the funding of clinical practice guidelines (CPGs) is formally reported. The aim of this study is to explore the accuracy and comprehensiveness of reporting on funding in German CPGs.

Methods

We searched for CPGs in the registry of the Association of the Scientific Medical Societies in Germany in July 2020. Information on guideline funding was categorised by two reviewers independently and discrepancies were clarified by discussion with a third reviewer. Accuracy and comprehensiveness of reporting on funding was assessed using the German Instrument for Methodological Guideline Appraisal (DELBI).

Results

We included 507 CPGs published between 2015 and 2020 in the main analysis. 23/507 (4.5%) of the CPGs achieved the highest DELBI score by including information on funding sources, expenses and the amount of funding provided, as well as a statement on the independence of the guideline authors from the funding institution(s). CPGs with more rigorous methodological requirements (systematic review of the literature and/or structured consensus-building) received higher DELBI scores.

Conclusion

German CPGs do not communicate their funding transparently. Transparency of CPG funding could be achieved by making it mandatory to publish information for all guidelines. For that purpose, a standardised form and guidance should be developed.
Hybrid cardiac telerehabilitation for coronary artery disease in Australia: a cost-effectiveness analysis
Authors: Senanayake Sameera , Halahakone Ureni , Abell Bridget , Kularatna Sanjeewa , McCreanor Victoria , McPhail Steven M. , Redfern Julie , Tom Briffa  , Parsonage William
Published: May 2023

Background

Traditional cardiac rehabilitation programs are centre-based and clinically supervised, with their safety and effectiveness well established. Notwithstanding the established benefits, cardiac rehabilitation remains underutilised. A possible alternative would be a hybrid approach where both centre-based and tele-based methods are combined to deliver cardiac rehabilitation to eligible patients. The objective of this study was to determine the long-term cost-effectiveness of a hybrid cardiac telerehabilitation and if it should be recommended to be implemented in the Australian context.

Methods

Following a comprehensive literature search, we chose the Telerehab III trial intervention that investigated the effectiveness of a long-term hybrid cardiac telerehabilitation program. We developed a decision analytic model to estimate the cost-effectiveness of the Telerehab III trial using a Markov process. The model included stable cardiac disease and hospitalisation health states and simulations were run using one-month cycles over a five-year time horizon. The threshold for cost-effectiveness was set at $AU 28,000 per quality-adjusted life-year (QALY). For the base analysis, we assumed that 80% completed the programme. We tested the robustness of the results using probabilistic sensitivity and scenario analyses.

Results

Telerehab III intervention was more effective but more costly and was not cost-effective, at a threshold of $28,000 per QALY. For every 1,000 patients who undergo cardiac rehabilitation, employing the telerehabilitation intervention would cost $650,000 more, and 5.7 QALYs would be gained, over five years, compared to current practice. Under probabilistic sensitivity analysis, the intervention was cost-effective in only 18% of simulations. Similarly, if the intervention compliance was increased to 90%, it was still unlikely to be cost-effective.

Conclusion

Hybrid cardiac telerehabilitation is highly unlikely to be cost-effective compared to the current practice in Australia. Exploration of alternative models of delivering cardiac telerehabilitation is still required. The results presented in this study are useful for policymakers wanting to make informed decisions about investment in hybrid cardiac telerehabilitation programs.
Impact of the Affordable Care Act on participation in the Supplemental Nutrition Assistance Program among low-income older Medicare beneficiaries
Authors: Kim Hyunmin , Mahmood Asos , Chang Cyril F. , Hammarlund Noah E. , Dobalian Aram
Published: May 2023

Background

The Affordable Care Act (ACA) provisions, especially Medicaid expansion, are believed to have “spillover effects,” such as boosting participation in the Supplemental Nutrition Assistance Program (SNAP) among eligible individuals in the United States (US). However, little empirical evidence exists about the impact of the ACA, with its focus on the dual eligible population, on SNAP participation. The current study investigates whether the ACA, under an explicit policy aim of enhancing the interface between Medicare and Medicaid, has improved participation in the SNAP among low-income older Medicare beneficiaries.

Methods

We extracted 2009 through 2018 data from the US Medical Expenditure Panel Survey (MEPS) for low-income (≤ %138 Federal Poverty Level [FPL]) older Medicare beneficiaries (n = 50,466; aged ≥ 65), and low-income (≤ %138 FPL) younger adults (aged 20 to < 65 years, n = 190,443). MEPS respondents of > %138 FPL incomes, younger Medicare and Medicaid beneficiaries, and older adults without Medicare were excluded from this study. Using a quasi-experimental comparative interrupted time-series design, we examined (1) whether ACA’s support for the Medicare-Medicaid dual-eligible program, through facilitating the online Medicaid application process, was associated with an increase in SNAP uptake among low-income older Medicare beneficiaries, and (2) in the instance of an association, to assess the magnitude of SNAP uptake that can be explicitly attributed to the policy’s implementation. The outcome, SNAP participation, was measured annually from 2009 through 2018. The year 2014 was set as the intervention point when the Medicare-Medicaid Coordination Office started facilitating Medicaid applications online for eligible Medicare beneficiaries.

Results

Overall, the change in the probability of SNAP enrollment from the pre- to post-intervention period was 17.4 percentage points higher among low-income older Medicare enrollees, compared to similarly low-income, SNAP-eligible, younger adults (β = 0.174, P < .001). This boost in SNAP uptake was significant and more apparent among older White (β = 0.137, P = .049), Asians (β = 0.408, P = .047), and all non-Hispanic adults (β = 0.030, P < .001).

Conclusions

The ACA had a positive, measurable effect on SNAP participation among older Medicare beneficiaries. Policymakers should consider additional approaches that link enrollment to multiple programs to increase SNAP participation. Further, there may be a need for additional, targeted efforts to address structural barriers to uptake among African Americans and Hispanics.
Prolactin receptor signaling induces acquisition of chemoresistance and reduces clonogenicity in acute myeloid leukemia
Authors: Cuesta-Casanovas Laia , Delgado-Martínez Jennifer , Cornet-Masana Josep M. , Carbó José M. , Banús-Mulet Antònia , Guijarro Francesca , Esteve Jordi , Risueño Ruth M.
Published: May 2023

Background

Development of precision medicine requires the identification of easily detectable and druggable biomarkers. Despite recent targeted drug approvals, prognosis of acute myeloid leukemia (AML) patients needs to be greatly improved, as relapse and refractory disease are still difficult to manage. Thus, new therapeutic approaches are needed. Based on in silico-generated preliminary data and the literature, the role of the prolactin (PRL)-mediated signaling was interrogated in AML.

Methods

Protein expression and cell viability were determined by flow cytometry. Repopulation capacity was studied in murine xenotransplantation assays. Gene expression was measured by qPCR and luciferase-reporters. SA-β-Gal staining was used as a senescence marker.

Results

The prolactin receptor (PRLR) was upregulated in AML cells, as compared to their healthy counterpart. The genetic and molecular inhibition of this receptor reduced the colony-forming potential. Disruption of the PRLR signaling, either using a mutant PRL or a dominant-negative isoform of PRLR, reduced the leukemia burden in vivo, in xenotransplantation assays. The expression levels of PRLR directly correlated with resistance to cytarabine. Indeed, acquired cytarabine resistance was accompanied with the induction of PRLR surface expression. The signaling associated to PRLR in AML was mainly mediated by Stat5, in contrast to the residual function of Stat3. In concordance, Stat5 mRNA was significantly overexpressed at mRNA levels in relapse AML samples. A senescence-like phenotype, measured by SA-β-gal staining, was induced upon enforced expression of PRLR in AML cells, partially dependent on ATR. Similar to the previously described chemoresistance-induced senescence in AML, no cell cycle arrest was observed. Additionally, the therapeutic potential of PRLR in AML was genetically validated.

Conclusions

These results support the role of PRLR as a therapeutic target for AML and the further development of drug discovery programs searching for specific PRLR inhibitors.
Systematic analysis of randomised controlled trials of Chinese herb medicine for non-alcoholic steatohepatitis (NASH): implications for future drug development and trial design
Authors: Chen Xianwen , Shi Junnan , Lai Yunfeng , Xue Yan , Ung Carolina Oi Lam , Hu Hao
Published: May 2023

Background

Non-alcoholic steatohepatitis (NASH) is a liver disease currently lacking an approved therapy, resulting in significant clinical demand. Traditional Chinese medicines (TCMs) have been commonly used to manage NASH. This study aimed to systematically analyse the randomised controlled trials (RCTs) using TCMs for NASH management.

Methods

A systematic literature review was performed by following PRISMA guidelines 2020 in six electronic databases: PubMed, Web of Science, Scopus, Embase, the Cochrane Library, and China National Knowledge Infrastructure, from inception until August 2022. RCTs using TCMs for NASH were included in the analysis, irrespective of language or blinding.

Results

112 RCTs were included in this review, with 10,573 NASH participants. 108 RCTs were conducted in China, and 4 RCTs were in other countries. Herbal medicine decoction was the major dosage form used for treating NASH (82/112). 11 TCMs products have been approved for NASH treatment (8 in China, 2 in Iran, and 1 in Japan). Classic prescriptions, such as “Huang Lian Jie Du decoction”, “Yin Chen Hao decoction”, and “Yi Guan Jian” were used in some studies. The TCMs treatment of NASH involved the use of 199 different plants, with the top 5 herbs being Salviae Miltiorrhizae Radix Et Rhizoma, Alismatis Rhizoma, Bupleuri Radix, Poria, and Curcumae Radix. “Salviae Miltiorrhizae Radix Et Rhizoma + Bupleuri Radix/Alismatis Rhizoma” were the mostly common drug-pair in the herbs network analysis. Nowadays, “Bupleuri Radix/Alismatis Rhizoma + Atractylodis Macrocephalae Rhizoma” are increasingly applied in herbal formulas for NASH. Based on the PICOS principles, the included studies varied in terms of the population, intervention, comparator, outcomes, and study design. However, some studies reported unstandardised results and failed to report diagnostic standards, inclusion or exclusion criteria, or sufficient patient information.

Conclusion

Adopting Chinese classic prescriptions or drug-pair may provide a basis for developing new drugs of NASH management. Further research is needed to refine the clinical trial design and obtain more convincing evidence for using TCMs to treat NASH.
Quality of anesthetist communication with surgical patients in the perioperative setting: a survey at an academic tertiary referral hospital in Ethiopia
Authors: Berhe Yophtahe Woldegerima , Agegnehu Temesgen , Endeshaw Mulualem , Riskey Nurhusen , Kassaw Getasew
Published: May 2023

Background

Effective communication is a fundamental step in providing best medical care and recognized as vital component of clinical anesthesia practice. Poor communication adversely affects patients’ safety and outcome. The objective of this study was to investigate the quality of anesthetist communication from patients’ perspectives at University of Gondar Comprehensive Specialized Hospital (UoGCSH), Northwest Ethiopia.

Methodology

A descriptive cross-sectional study was conducted on 423 surgical patients from April 1, – May 30, 2021. Perioperative patient-anesthetist communication (PPAC) was measured by using 15-items Communication Assessment Tool graded by 5-points Likert scale. Data collection was executed during postoperative time as the patients were optimally recovered from anesthesia. The collected data were cleaned and descriptive analysis was performed.

Results

A total of 400 (94.6% response rate) patients included and 226 (56.7%) were female. The median (IQR) age was 30 (25 – 40) years. Three-hundreds and sixty-one (90.3%) patients had reported good PPAC and 39 (9.8%) reported poor PPAC. The median (IQR) of PPAC scores was 53.0 (48.0 – 57.0) and range from 27 to 69. Highest mean score was observed for the item “Talked in terms I could understand” (4.3 ± 0.7). Lowest mean scores were observed for the item “Checked to be sure I understood everything” (1.9 ± 0.9). Patients who had underwent emergency surgery, no previous anesthetic exposure, had significant preoperative anxiety, no history of previous hospital admission, and moderate-severe preoperative pain were found to have poor PPAC compared to their counterparts in the proportions of 82.1%, 79.5%, 69.2%, 64.1%, and 59.0% respectively.

Conclusions

There was good PPAC in our hospital from patients’ perspective. However, there should be improvements in checking the degree of understanding of the delivered information, encouraging to question, disclosing next steps and involving in decision-making. Patients who underwent emergency surgery, had no previous anesthetic exposure, had clinically significant level of preoperative anxiety, had no history of previous hospital admission, and had moderate-severe preoperative pain were found to have poor PPAC.
Epigenetically silenced lncRNA SNAI3-AS1 promotes ferroptosis in glioma via perturbing the m6A-dependent recognition of Nrf2 mRNA mediated by SND1
Authors: Zheng Jianglin , Zhang Qing , Zhao Zhen , Qiu Yue , Zhou Yujie , Wu Zhipeng , Jiang Cheng , Wang Xuan , Jiang Xiaobing
Published: May 2023

Background

Ferroptosis has been linked to tumor progression and resistance to antineoplastic therapy. Long noncoding RNA (lncRNA) exerts a regulatory role in various biological processes of tumor cells, while the function and molecular mechanism of lncRNA in ferroptosis are yet to be clarified in glioma.

Methods

Both gain-of-function and loss-of-function experiments were employed to investigate the effects of SNAI3-AS1 on the tumorigenesis and ferroptosis susceptibility of glioma in vitro and in vivo. Bioinformatics analysis, Bisulfite sequencing PCR, RNA pull-down, RIP, MeRIP and dual-luciferase reporter assay were performed to explore the low expression mechanism of SNAI3-AS1 and the downstream mechanism of SNAI3-AS1 in ferroptosis susceptibility of glioma.

Results

We found that ferroptosis inducer erastin downregulates SNAI3-AS1 expression in glioma by increasing the DNA methylation level of SNAI3-AS1 promoter. SNAI3-AS1 functions as a tumor suppressor in glioma. Importantly, SNAI3-AS1 enhances the anti-tumor activity of erastin by promoting ferroptosis both in vitro and in vivo. Mechanistically, SNAI3-AS1 competitively binds to SND1 and perturbs the m6A-dependent recognition of Nrf2 mRNA 3’UTR by SND1, thereby reducing the mRNA stability of Nrf2. Rescue experiments confirmed that SND1 overexpression and silence can rescue the gain- and loss-of-function ferroptotic phenotypes of SNAI3-AS1, respectively.

Conclusions

Our findings elucidate the effect and detailed mechanism of SNAI3-AS1/SND1/Nrf2 signalling axis in ferroptosis, and provide a theoretical support for inducing ferroptosis to improve glioma treatment.
A rapid and visual detection assay for Clonorchis sinensis based on recombinase polymerase amplification and lateral flow dipstick
Authors: Ma Xiaoxiao , Bai Xue , Li Hongchang , Ding Jing , Zhang Huiyuan , Qiu Yangyuan , Wang Jing , Liu Xiaolei , Liu Mingyuan , Tang Bin , Xu Ning
Published: May 2023

Background

Fish-borne zoonotic clonorchiasis, caused by Clonorchis sinensis, is an emerging public health problem in several countries with more than 15 million people infected globally. However, a lack of accurate point-of-care (POC) diagnostic tests in resource-limited areas is still a critical barrier to effective treatment and control of clonorchiasis. The development of the recombinase polymerase amplification(RPA) assay, a POC diagnostic test based on the amplification of pathogen DNA, has provided a new, simple and inexpensive tool for disease detection with high sensitivity and specificity.

Methods

A novel RPA method was developed based on specific primers and probes, and combined with the dipstick, to allow for the rapid and intuitive detection of C. sinensis through the amplification of the mitochondrial cytochrome c oxidase subunit 1 (COX1) gene. The lower limit of detection for the combined RPA/lateral flow dipstick (RPA-LFD) assay was evaluated using dilutions of the target DNA sequence. Cross-reactivity was evaluated using genomic DNA from 10 additional control parasites. Forty human clinical stool samples were tested to verify its performance.

Results

The evaluated primers designed from the C. sinensisCOX1 region can be used to detect adult worms, metacercariae, and eggs at 39 °C within 20 min, and the results can be visually observed using the LFD. The detection limit of pathogen genomic DNA was as low as 10 fg, and the number of metacercaria(e) in fish and egg(s) in faeces were both as low as one. This improved the sensitivity of low-infection detection tremendously. The test is species-specific, and no other related control parasites were detected. In human stool samples with eggs per gram (EPG) > 50, the RPA-LFD assay was performed consistent with conventional Kato-Katz (KK) and PCR methods.

Conclusion

The established RPA-LFD assay provides a powerful tool for the diagnosis and epidemiological survey of C. sinensis from human and animal samples, and has important implications for the effective control of clonorchiasis.

Graphical Abstract
Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study
Authors: Mosch Benjamin , Hagena Verena , Herpertz Stephan , Diers Martin
Published: May 2023

Background

Previous studies have repeatedly found distinct brain morphometric changes in patients with fibromyalgia (FM), mainly affecting gray and white matter abnormalities in areas related to sensory and affective pain processing. However, few studies have thus far linked different types of structural changes and not much is known about behavioral and clinical determinants that might influence the emergence and progression of such changes.

Methods

We used voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) to detect regional patterns of (micro)structural gray (GM) and white matter (WM) alterations in 23 patients with FM compared to 21 healthy controls (HC), while considering the influence of demographic, psychometric, and clinical variables (age, symptom severity, pain duration, heat pain threshold, depression scores).

Results

VBM and DTI revealed striking patterns of brain morphometric changes in FM patients. Bilateral middle temporal gyrus (MTG), parahippocampal gyrus, left dorsal anterior cingulate cortex (dACC), right putamen, right caudate nucleus, and left dorsolateral prefrontal cortex (DLPFC) showed significantly decreased GM volumes. In contrast, increased GM volume was observed in bilateral cerebellum and left thalamus. Beyond that, patients displayed microstructural changes of WM connectivity within the medial lemniscus, corpus callosum, and tracts surrounding and connecting the thalamus. Sensory-discriminative aspects of pain (pain severity, pain thresholds) primarily showed negative correlations with GM within bilateral putamen, pallidum, right midcingulate cortex (MCC), and multiple thalamic substructures, whereas the chronicity of pain was negatively correlated with GM volumes within right insular cortex and left rolandic operculum. Affective-motivational aspects of pain (depressive mood, general activity) were related to GM and FA values within bilateral putamen and thalamus.

Conclusions

Our results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula.
Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression
Authors: Jahn Ulrika , Garske-Román Ulrike , Sandström Mattias , Lubberink Mark , Sundin Anders
Published: May 2023

Background

The accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.

Method

Patients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.

Results

There was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.

Conclusion

In this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.
Two decades of epidemiological surveillance of the pine wood nematode in France reveal its absence despite suitable conditions for its establishment
Authors: Mariette Nicolas , Hotte Hoël , Chappé Anne-Marie , Grosdidier Marie , Anthoine Géraldine , Sarniguet Corinne , Colnard Odile , Kersaudy Emmanuel , Paris Marie-Thérèse , Koen Emmanuel , Folcher Laurent
Published: May 2023

Key message

This study takes stock of the first 20 years (2000–2019) of monitoring the pine wood nematode (PWN) in metropolitan France. While PWN was never found in the wild during this period, it was reported in some wood-based commodities entering or circulating on French territory. This stresses the importance of remaining extremely vigilant, as the conditions found in France, especially weather conditions, could be particularly suitable for the pest’s establishment.

Context

The pine wood nematode (PWN) Bursaphelenchus xylophilus, responsible for pine wilt disease (PWD), is one of the most important forest tree pests worldwide. It is thus the focus of many monitoring programmes. In the European Union, for example, it is categorised as a priority quarantine pest, so each member state is obliged to monitor the PWN on its territory.

Aims

The first objective of this paper was to describe PWN monitoring in metropolitan France, namely how it is organised and whether it has led to the nematode’s detection. Secondly, we wished to investigate what the levels of PWD expression for host pines infected by B. xylophilus would be in France. Thirdly, we wanted to find out whether other Bursaphelenchus species had been found on French territory during these two decades of PWN monitoring.

Methods

We analysed data from samples collected in the framework of the monitoring programme between 2000 and 2019 to track the PWN in its host pines, its insect vector (Monochamus spp.) and in wood-based commodities imported into or circulating in metropolitan France. We also generated risk maps of PWD expression based on an evapo-transpiration model using climate data for the period 2000–2019.

Results

This monitoring, which was regularly reinforced from 2000 to 2019, consisted of sampling and analysing around 18,000 wood samples and 66,000 insects over this period. Although the PWN was not detected in pine stands or within its insect vector, some wood-based commodities were found to be contaminated. Risk maps of PWD expression show that in the most recent years (2015–2019), the weather conditions in a large fraction of metropolitan France were suited to PWD expression, mostly with a delay (i.e., latency) between infection and observable wilt symptoms. PWN monitoring has also revealed the presence of other Bursaphelenchus species, most of which were discovered for the first time in metropolitan France and are described herein.

Conclusion

While metropolitan France is still free of the PWN, this study emphasises the need to remain cautious as the French territory appears particularly suitable for this pest’s establishment. Furthermore, our research has led us to propose some ideas on how to improve PWN monitoring.
An improved dynamic programming tracking-before-detection algorithm based on LSTM network
Authors: Song Fei , Li Yong , Cheng Wei , Dong Limeng
Published: May 2023

The detection and tracking of small and weak maneuvering radar targets in complex electromagnetic environments is still a difficult problem to effectively solve. To address this problem, this paper proposes a dynamic programming tracking-before-detection method based on a long short-term memory (LSTM) network (LSTM-DP-TBD). With the predicted target motion state provided by the LSTM network, the state transition range of the traditional DP-TBD algorithm can be updated in real time, and the detection and tracking effect achieved for maneuvering small and weak targets is also improved. Utilizing the LSTM network to model the moving state of the target, the moving features of the maneuvering target can be learned from the noisy input data. By incorporating these features into the traditional DP-TBD algorithm, the state transition set can be adjusted in time with the changes in the moving state of the target so that the new algorithm is capable of effectively recursively accumulating the movement trend of the maneuvering small and weak target. Simulation results show that the new algorithm is able to effectively accomplish the task of detecting and tracking maneuvering small and weak targets, and it achieves improved detection and tracking probabilities.
Chromosome folding and prophage activation reveal specific genomic architecture for intestinal bacteria
Authors: Lamy-Besnier Quentin , Bignaud Amaury , Garneau Julian R. , Titecat Marie , Conti Devon E. , Von Strempel Alexandra , Monot Marc , Stecher Bärbel , Koszul Romain , Debarbieux Laurent , Marbouty Martial
Published: May 2023

Background

Bacteria and their viruses, bacteriophages, are the most abundant entities of the gut microbiota, a complex community of microorganisms associated with human health and disease. In this ecosystem, the interactions between these two key components are still largely unknown. In particular, the impact of the gut environment on bacteria and their associated prophages is yet to be deciphered.

Results

To gain insight into the activity of lysogenic bacteriophages within the context of their host genomes, we performed proximity ligation-based sequencing (Hi-C) in both in vitro and in vivo conditions on the 12 bacterial strains of the OMM12 synthetic bacterial community stably associated within mice gut (gnotobiotic mouse line OMM12). High-resolution contact maps of the chromosome 3D organization of the bacterial genomes revealed a wide diversity of architectures, differences between environments, and an overall stability over time in the gut of mice. The DNA contacts pointed at 3D signatures of prophages leading to 16 of them being predicted as functional. We also identified circularization signals and observed different 3D patterns between in vitro and in vivo conditions. Concurrent virome analysis showed that 11 of these prophages produced viral particles and that OMM12 mice do not carry other intestinal viruses.

Conclusions

The precise identification by Hi-C of functional and active prophages within bacterial communities will unlock the study of interactions between bacteriophages and bacteria across conditions (healthy vs disease).
Distribution of surface heat flow and effects on the subsurface temperatures in the northern part of Thrace Basin, NW Turkey
Authors: Erkan Kamil , Balkan-Pazvantoğlu Elif
Published: May 2023

The Thrace Basin in northwestern Turkey is a deep Eocene–Oligocene hydrocarbon-bearing sedimentary basin. The basin has potential for geothermal energy utilization in the future due to its favorable geological conditions. In this study, we combined the available bottom hole temperature (BHT) data from 70 points with the thermal conductivity and radiogenic heat productions of the basin formations, and generated a detailed thermal model of the northern part of the basin. For heat flow determinations from the BHT data, we applied Bullard’s thermal resistance method on formation thermal conductivities and thicknesses. The results give an average surface heat flow of 65.8 ± 11.3 mW/m2. We obtained high heat flow values (75–80 mW/m2) in the eastern and western sides, and the central part of the study area. These relatively high heat flow values can be explained by the combined effect of basement topography and the variations in the radiogenic heat production of the basement rocks. The calculated subsurface temperatures in selected hydrocarbon fields vary in the range of 45–64 °C at 1 km depth, 99–136 °C at 3 km depth, and 155–208 °C at 5 km depth as a result of local variations of the surface heat flow and formation thermal resistances. These variations in subsurface temperatures can have significant effects on the cost of geothermal energy production in future.
Non-indigenous preschool teachers’ culturally relevant pedagogy in the indigenous areas of Taiwan
Authors: Chen Bi-Ching
Published: May 2023

This study used the Ladson-Billings culturally relevant pedagogical approach to understanding non-indigenous preschool teachers’ multicultural literacy and practices in indigenous areas. Through purposive sampling, we selected six teachers with three years of teaching experience each in Eastern Taiwan as study participants. Interviews with them, classroom observation records, teaching files, students’ diaries, and researchers’ inspiring diaries were all used as data sources. The analyses were based on the Ladson-Billings culturally relevant pedagogical approach. There were three major results. First, non-indigenous teachers used indigenous language and culture and invited indigenous parents to cooperate with the tribe to increase their students’ academic achievement. Second, the teachers connected their indigenous students’ families’ backgrounds and experiences with their curriculums, maintained certain indigenous cultural norms in the classroom, and communicated with indigenous students’ parents in languages that were familiar to them. Third, the teachers devised strategies to overcome the gap between their teaching goals and beliefs about their students’ childcare centers and cultural backgrounds. The factor that most contributed to the success of non-indigenous preschool teachers teaching in indigenous was communicating with indigenous parents and encouraging them to join in school activities.
Pathological complete response with nivolumab for recurrence of liver metastasis after gastrectomy of gastric cancer
Authors: Jun Chen , Yamauchi Suguru , Yube Yukinori , Egawa Hiroki , Yoshimoto Yutaro , Kubota Akira , Tsuda Kenki , Kaji Sanae , Orita Hajime , Oka Shinichi , Mine Shinji , Fukunaga Tetsu
Published: May 2023

Background

Advanced gastric cancer has an unfavorable prognosis and poor curability. Immune checkpoint inhibitors, such as nivolumab, have recently emerged as a potential solution for this aggressive disease. However, there is a lack of established evidence on the clinical efficacy of these agents, particularly in the perioperative period for advanced gastric cancer patients who are unresectable, recurrent, or preoperative. Despite the limited data available, there have been rare cases of dramatic therapeutic effects. In this study, we present a successful case of nivolumab treatment along with surgery.

Case presentation

A 69-year-old female presented with pericardial discomfort and was diagnosed with advanced gastric cancer following upper gastrointestinal endoscopy. Laparoscopic distal gastrectomy with D2 lymph node dissection was performed, resulting in a final pathological diagnosis of Stage IIIA. The patient received postoperative adjuvant chemotherapy with oral S-1 therapy, but was found to have multiple liver metastases at 8 months postsurgery. Weekly paclitaxel and ramucirumab therapy was initiated, but the patient experienced adverse side effects, leading to the discontinuation of treatment. Nivolumab monotherapy was then administered for 18 cycles, resulting in a partial therapeutic response and PET–CT revealed a complete metabolic response. However, the patient developed a Grade 3 pemphigoid as an immune-related adverse event, leading to the cessation of nivolumab. The patient underwent laparoscopic partial hepatectomy. Postoperative pathology showed no residual tumor cells, indicating a complete response. At present, 25 months after surgery, the patient was alive without recurrence.

Conclusion

In this report, we present a case of gastric cancer with liver metastatic recurrence, in which a complete pathological response was achieved with nivolumab treatment. Although determining whether surgical intervention is necessary following successful drug treatment can be challenging, PET–CT imaging may be useful in decision-making regarding surgical treatment.
Exertional Heat Stroke and Rhabdomyolysis: A Medical Record Review and Patient Perspective on Management and Long-Term Symptoms
Authors: Kruijt Nick , van den Bersselaar L. R. , Hopman M. T. E. , Snoeck M. M. J. , van Rijswick M. , Wiggers T. G. H. , Jungbluth H. , Bongers C. C. W. G. , Voermans N. C.
Published: May 2023

Introduction

Exertional heat stroke (EHS) is a medical emergency, occurring when the body generates more heat than it can dissipate, and frequently associated with exertional rhabdomyolysis (ERM). In the present study we aimed to (I) identify clinical features and risk factors, (II) describe current prehospital management, (III) investigate long-term outcomes including the impact on mental health, and review the guidance received during restarting activities. We hope that our approach will improve individual and organizational heat illness preparedness, and improve follow-up care.

Methods

We performed a prospective online survey and retrospective medical record review among athletes and military personnel with an episode of EHS/ERM in the Netherlands between 2010 and 2020. We evaluated prehospital management, risk factors, clinical features and long-term outcomes at 6 and 12 months after the event, including mental health symptoms. Furthermore, we investigated what guidance participants received during follow-up, and assessed the patients’ perspective on these outcomes.

Results

Sixty participants were included, 42 male (70%) and 18 female (30%), of which 47 presented with EHS (78%) and 13 with ERM (22%). Prehospital management was inconsistent and in the majority of participants not conducted according to available guidelines. Self-reported risk factors included not feeling well-acclimatized to environmental heat (55%) and peer pressure (28%). Self-reported long-term symptoms included muscle symptoms at rest (26%) or during exercise (28%), and neurological sequelae (11%). Validated questionnaires (CIS, HADS and SF-36) were indicative of severe fatigue (30%) or mood/anxiety disorders (11%). Moreover, 90% expressed a lack of follow-up care and that a more frequent and intensive follow-up would have been beneficial for their recovery process.

Conclusion

Our findings indicate major inconsistencies in the management of patients with EHS/ERM, emphasizing the compelling need for implementing standardized protocols. Based on the results of long-term outcome measures, we recommend to counsel and evaluate every patient not only immediately after the event, but also in the long-term.
Occurrence of plant pathogenic Pseudomonas syringae in the Danube River Basin: abundance and diversity assessment
Authors: Anteljević Marina , Rosić Iva , Medić Olja , Kolarević Stoimir , Berić Tanja , Stanković Slaviša , Nikolić Ivan
Published: May 2023

Plant pathogenic strains of Pseudomonas syringae (Psy) spp. have been detected in nonagricultural habitats, including those associated with the water cycle. Their presence in aquatic systems allows dissemination over long distances, especially with irrigation practices. In May 2021, we sampled 15 sites along the Danube River Basin in Serbia to gain insight into P. syringae abundance and diversity. We identified 79 Psy strains using Psy-specific primers, and a partial sequence of the citrate synthase (cts) house-keeping gene has served for phylogenetic diversity assessments. Phenotypic diversity determination included characterizing features linked with survival and pathogenic lifestyle. The ice nucleation activity, pectinolytic activity, swimming and swarming assays, and hypersensitive reaction on plants were tested. Psy was detected at ten of 15 sites examined at abundance ranging from 1.0 × 102 to 1.2 × 104 CFU/L. We discovered the presence of four phylogroups, with phylogroup 2 being the most abundant, followed by phylogroups 7, 9, and 13. The hypersensitive reaction was induced by 68.63% of the isolates from the collection. A partial sequence comparison of the cts gene showed 100% similarity between isolates from cherry plants epidemics in Serbia caused by Psy and isolates from the Danube River. Our results suggest that the Danube River, extensively used for irrigation of agricultural fields, harbors diverse strains of Psy, which possess various features that could lead to potential disease outbreaks on crops. This study represents the first in-depth analysis of Psy abundance and diversity in the Danube River Basin. It sets the ground for future pre-epidemic studies and seasonal monitoring of Psy population dynamics.