bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid and selective on-site detection of triacetone triperoxide based on visual colorimetric method
Authors: Li Yonggang , Liu Xingsheng , Zhang Guannan , Wang Ruihua , Yue Ruimin , Liao Guangfu , Sun Zhenwen , Liu Yao
Published: August 2022

In this work, a visual colorimetric method for the rapid and selective detection of triacetone triperoxide is reported. This visual colorimetric method is based on the reaction between potassium titanyl oxalate and hydrogen peroxide (H2O2) released from triacetone triperoxide degradation. Potassium titanyl oxalate can selectively react with H2O2 to form peroxo-titanic acid (an orange complex), enabling the colorimetric detection of triacetone triperoxide. Based on the theory that triacetone triperoxide produces hydrogen peroxide under acidic conditions, acid types, acid concentration, response time, visual limit of detection, and reactants ratio are systematically studied simultaneously for this colorimetric method. Under sulfuric acid concentration is 60%, the proposed method can almost detect triacetone triperoxide instantly, and the color of the solution reaches the maximum within 1 min and remains stable with a visual limit of detection as low as 3.0 × 10−5 mol/L. Interference experiments were carried out on other kinds of explosives (hexamethylene triperoxide diamine, trinitrotoluene, etc.). The use of colorimetric card brings great convenience to the rapid, qualitative, and semi-quantitative on-site detection of triacetone triperoxide. Because of its rapidity, high sensitivity, simplicity, and selectivity, the proposed visual colorimetric method can serve as a valuable and promising reference for triacetone triperoxide’s rapid, qualitative on-site detection.
Social Studies Instruction With Educational Music: Write, Compose, and Apply
Authors: Egüz Şule
Published: August 2022

The present study aimed to assist pre-service social studies teachers in the production of song lyrics adequate for the curriculum, composition of songs that would be of interest for secondary school students to construct functional educational music in social studies courses and determine the impact of this music on academic achievements and learning processes of the students. In the present study, exploratory sequential design, a mixed research method, was employed. In the first stage, song lyrics were written by 55 pre-service teachers attending the education department in a public university in Malatya province, Turkey, and songs were composed with these lyrics by a music teacher, and two music department students. The second stage (application phase) was conducted with 48 secondary school students. In the final stage, the views on the use of educational songs in the classroom were obtained. The study data were analyzed with quantitative and qualitative analysis techniques. The study findings demonstrated that the songs created by pre-service teachers improved the achievements of secondary school students in the social studies course, supported learning by fun, provided better comprehension of the course topics, and were effective in maintaining the student motivation and attention.
Business for peace: How entrepreneuring contributes to Sustainable Development Goal 16
Authors: Gallo Peter Jack , Sosa Santiago , Velez-Calle Andres
Published: August 2022

We examine entrepreneurial ventures in a post-conflict context to identify practices that are helpful for companies operating in conflict zones while contributing to the United Nations’ Sustainable Development Goal 16 (SDG 16)—Peace, Justice, and Strong Institutions. Using emancipatory entrepreneuring as our theoretical lens, we analyze entrepreneurial ventures where ex-combatants seek to create economic opportunities and challenge the status quo of violence, poverty, and inequality in their rural communities. We develop four qualitative case studies of ex-combatant entrepreneurship to identify the activities that enable them to grow their businesses while promoting peace. We identify actor distance and entrepreneurial stage as key dimensions for defining a matrix of relationship arrangements that facilitate venture success and peacebuilding efforts. We conclude with a summary of our contributions and implications for research and practice.

JEL Classifications: D63, D74, H56, L14, L26
The construction of the responsible patient in complex palliative care: interpreting palliative care policies
Authors: Thoresen Lisbeth , Røberg Anne-Stine Bergquist
Published: August 2022

Background:

To contribute with knowledge to health policy development, this article presents a critical discourse analysis of two Norwegian official reports on palliative care published in 1999 and 2017.

Methods:

We identify, describe and discuss how linguistic features in policy documents contribute to and engender a distinct change from 1999 to 2017 in how patients are framed, documenting the development of palliative care.

Results:

The analysis identifies and considers two interwoven discourses: the discourse of accountability and the discourse of complexity. The patient moves from being described as in need of care, in the 1999 report, to being described as an active and responsible patient making proper choices, in the 2017 report.

Conclusion:

Result of this policy development might be less involvement of professionals and focus on existential questions, and more responsibility on patients for their prospective wellbeing and health: a change that we argue should be considered and counteracted in upcoming policy processes considering palliative care.
Impact of fremanezumab on disability outcomes in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies
Authors: McAllister Peter , Cohen Joshua M. , Campos Verena Ramirez , Ning Xiaoping , Janka Lindsay , Barash Steve
Published: August 2022

Background

Migraine is the second leading cause of disability worldwide. Although many preventive treatments reduce migraine frequency and severity, it is unclear whether these treatments reduce migraine-related disability in a clinically meaningful way. This pooled analysis evaluated the ability of fremanezumab to reduce migraine-related disability, based on responses and shifts in severity in patient-reported disability outcomes.

Methods

This pooled analysis included 3 double-blind phase 3 trials (HALO EM, HALO CM, FOCUS) in which patients with episodic or chronic migraine were randomly assigned 1:1:1 to quarterly or monthly fremanezumab or matched placebo for 12 weeks. Migraine-related disability was assessed using the 6-item Headache Impact Test (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaires. A clinically meaningful improvement in disability was defined per American Headache Society guidelines: for HIT-6, a ≥ 5-point reduction; for MIDAS, a ≥ 5-point reduction when baseline score was 11 to 20 or ≥ 30% reduction when baseline score was > 20. Proportions of patients who demonstrated shifts in severity for each outcome were also evaluated.

Results

For patients with baseline MIDAS scores of 11 to 20 (n = 234), significantly higher proportions achieved 5-point reductions from baseline in MIDAS scores with fremanezumab (quarterly, 71%; monthly, 70%) compared with placebo (49%; both P ≤ 0.01). For patients with baseline MIDAS scores of > 20 (n = 1266), proportions achieving ≥30% reduction from baseline in MIDAS scores were also significantly higher with fremanezumab (quarterly, 69%; monthly, 79%) compared with placebo (58%; both P < 0.001). For HIT-6 scores, proportions of patients achieving 5-point reductions from baseline were significantly higher with fremanezumab (quarterly, 53%; monthly, 55%) compared with placebo (39%; both P < 0.0001). Proportions of patients with shifts of 1 to 3 grades down in MIDAS or HIT-6 disability severity were significantly greater with quarterly and monthly fremanezumab compared with placebo (all P < 0.0001).

Conclusion

Fremanezumab demonstrated clinically meaningful improvements in disability severity in this pooled analysis.

Trial registrations

HALO CM, NCT02621931; HALO EM, NCT02629861; FOCUS, NCT03308968.
Temporal variations in the pattern of breathing: techniques, sources, and applications to translational sciences
Authors: Oku Yoshitaka
Published: August 2022

The breathing process possesses a complex variability caused in part by the respiratory central pattern generator in the brainstem; however, it also arises from chemical and mechanical feedback control loops, network reorganization and network sharing with nonrespiratory motor acts, as well as inputs from cortical and subcortical systems. The notion that respiratory fluctuations contain hidden information has prompted scientists to decipher respiratory signals to better understand the fundamental mechanisms of respiratory pattern generation, interactions with emotion, influences on the cortical neuronal networks associated with cognition, and changes in variability in healthy and disease-carrying individuals. Respiration can be used to express and control emotion. Furthermore, respiration appears to organize brain-wide network oscillations via cross-frequency coupling, optimizing cognitive performance. With the aid of information theory-based techniques and machine learning, the hidden information can be translated into a form usable in clinical practice for diagnosis, emotion recognition, and mental conditioning.
Hepatitis B, C, and delta in the general population in Mayotte: hepatitis B as a major public health concern
Authors: Brouard Cécile , Parenton Fanny , Youssouf Hassani , Chevaliez Stéphane , Gordien Emmanuel , Jean Maxime , Bruyand Mathias , Vaux Sophie , Lot Florence , Ruello Marc ,   Unono Wa Maore group, Fleury Marion , Richard Jean-Baptiste , Solet Jean-Louis , Filleul Laurent , Jezewski-Serra Delphine , Chesneau Julie
Published: August 2022

Background

Located in southwestern Indian Ocean, Mayotte is a French territory, with a very specific demographic, social and health context. To date, epidemiological data on infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses in Mayotte have been sparse. We aimed to estimate, in the 15–69-year-old general population living in Mayotte, the prevalence of infections by hepatitis B (HBV), C (HCV), and delta (HDV) viruses and the distribution of HBV status: current infection with positive HBs antigen (Ag); resolved infection with positive HBc antibodies and negative HBsAg; immunisation by vaccination with only positive HBs antibodies; and no infection/no immunisation with negative markers. We also described the characteristics of infected people and assessed the determinants of lifetime HBV infection.

Methods

The Unono Wa Maore survey, implemented in a random sample of the general population in 2018–2019, consisted of an at-home collection of epidemiological data and venous blood samples. Detection of hepatitis B, C, and delta serological and molecular markers was performed.

Results

Among 5207 eligible people, 4643 responded to the questionnaire (89.2%), with 2917 being tested for HBV and HCV (62.8%). Estimated HBV status was as follows: current infection 3.0% (95% confidence interval [CI]: 2.3–3.9%) (n = 76); resolved infection 27.8% (95% CI: 25.8–29.9); immunisation by vaccination 27.7% (95% CI: 25.9–29.7); and no infection/no immunisation 41.5% (95% CI: 39.3–43.7). One participant was positive for HDV antibodies (Ab) (0.65%) with a negative HDV-RNA viral load. The risk of lifetime HBV infection was higher in men (adjusted prevalence ratio (aPR): 1.55, 95% CI: 1.29–1.89); in people aged 30–49 years (aPR: 3.83, 95% CI: 1.49–9.81) or 50–69 years (aPR: 4.52, 95% CI: 1.77–11.53) compared to those under 20; in individuals who reported no condom use during their first sexual intercourse (aPR: 1.46, 95% CI: 1.01–2.14); and in those living in Dembeni-Mamoudzou (aPR: 1.40, 95% CI: 1.09–1.80) compared to the West-Centre of Mayotte. Finally, six individuals were positive for HCV antibodies (0.21%), including three positive for HCV RNA.

Conclusions

Mayotte is an area of intermediate endemicity for HBV and low endemicity for HCV and HDV. With a prevalence of HBsAg 10 times higher than in mainland France, a high proportion of people susceptible to HBV infection, and a demographic, health, and social context that may favour its transmission, hepatitis B is a major public health concern in Mayotte.
Impact of COVID-19 restrictive measures on income and health service utilization of tuberculosis patients in India
Authors: Chatterjee Susmita , Das Palash , Vassall Anna
Published: August 2022

Background

The nationwide lockdown (March 25 to June 8, 2020) to curb the spread of coronavirus infection had significant health and economic impacts on the Indian economy. There is limited empirical evidence on how COVID-19 restrictive measures may impact the economic welfare of specific groups of patients, e.g., tuberculosis patients. We provide the first such evidence for India.

Methods

A total of 291 tuberculosis patients from the general population and from a high-risk group, patients from tea garden areas, were interviewed at different time points to understand household income loss during the complete lockdown, three and eight months after the complete lockdown was lifted. Income loss was estimated by comparing net monthly household income during and after lockdown with prelockdown income. Tuberculosis service utilization patterns before and during the lockdown period also were examined. Household income loss, travel and other expenses related to tuberculosis drug pickup were presented in 2020 US dollars (1 US$ = INR 74.132).

Results

26% of households with tuberculosis patients in tea garden areas and 51% of households in the general population had zero monthly income during the complete lockdown months (April–May 2020). Overall income loss slowly recovered during July–August compared to April–May 2020. Approximately 7% of patients in the general population and 4% in tea garden areas discontinued their tuberculosis medicines because of the complete lockdown.

Conclusion

Discontinuation of medicine will have an additional burden on the tuberculosis elimination program in terms of additional cases, including multidrug resistant tuberculosis cases. Income loss for households and poor restoration of income after the lockdown will likely have an impact on the nutrition of tuberculosis patients and families. Tuberculosis patients working in the informal sector were the worst affected group during the nationwide lockdown. This emphasizes that a policy priority must continue to protect those working in informal sectors from the economic consequences of such restrictive measures, including paid sick leave, additional food support, and direct benefit transfers. Alongside ensuring widespread access to COVID-19 vaccines, these policy actions remain pivotal in ensuring the well-being of those who are unfortunate enough to be living with tuberculosis.
Coupled plasma filtration adsorption for the treatment of sepsis or septic shock: a systematic review and meta-analysis
Authors: Li Yuting , Li Hongxiang , Guo Jianxing , Wang Youquan , Zhang Dong
Published: August 2022

Background

The effect of coupled plasma filtration adsorption (CPFA) for the treatment of sepsis or septic shock is controversial. A systematic review and meta-analysis was performed to evaluate the impact of CPFA on all-cause mortality in patients with sepsis or septic shock.

Methods

We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of May 2022. We included studies involving patients (˃ 14 years) with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality (hospital mortality, 28-day mortality or 30-day mortality). Results were expressed as odds ratio (OR) with accompanying 95% confidence interval (CI).

Results

Six studies including 537 patients were included. The primary outcome of this meta-analysis showed that the all-cause mortality was about 54.2% (119/243 in the CPFA group and 172/294 in the control group). There was no statistically significant difference in the all-cause mortality between two groups (odds ratio [OR] = 0.75; 95% CI 0.53 to 1.06; P = 0.11; Chi2 = 14.04; I2 = 64%).

Conclusions

The treatment of CPFA failed to decrease all-cause mortality of sepsis or septic shock patients. Further large-scale randomized controlled trials (RCTs) evaluating the ability of this therapy to improve clinical outcomes are still required to confirm these results.
Identification and functional analysis of LncRNA-XIST ceRNA network in prostate cancer
Authors: Wang Jie , Huang Jie , Guo Yingxue , Fu Yuli , Cao Yifang , Zhou Kang , Ma Jianxiong , Lv Bodong , Huang Wenjie
Published: August 2022

Background

Long non-coding RNAs (lncRNAs) play a functional role in the progression of prostate cancer (PCa). However, the molecular mechanism, expression, or function of the lncRNA XIST in PCa is not well understood. Therefore, the major goal of this study was to investigate the involvement of XIST in PCa.

Methods

We used the The Cancer Genome Atlas (TCGA) database to conduct a pan-cancer bioinformatics analysis of XIST and identified that it may play an important role in prostate cancer. This finding was verified using clinical samples and in vitro assays. Finally, we constructed an XIST ceRNA network for prostate cancer.

Results

Our in vitro and in vivo results showed that the XIST gene expression level was higher in PCa derived cells and tissues compared to that in normal cells and tissues. XIST gene expression level was positively correlated with the invasion and proliferation of tumour cells. Furthermore, the downregulation of XIST inhibited the growth of subcutaneous 22Rv1 xenografts in nude mice. In addition, we constructed a XIST ceRNA network. Consistent with previous studies, we found that the role of XIST is mediated through via sponges, such as miRNA -96-5p, miRNA -153-3p, and miRNA-182-5p.

Conclusion

High expression level of XIST can lead to enhanced carcinogenicity in PCa. Therefore, XIST has the potential to be used as a prognostic marker and may become a new research focus for the treatment of PCa.
Enhancing health and wellness by, for and with Indigenous youth in Canada: a scoping review
Authors: Okpalauwaekwe Udoka , Ballantyne Clifford , Tunison Scott , Ramsden Vivian R.
Published: August 2022

Background

Indigenous youth in Canada face profound health inequities which are shaped by the rippling effects of intergenerational trauma, caused by the historical and contemporary colonial policies that reinforce negative stereotypes regarding them. Moreover, wellness promotion strategies for these youth are replete with individualistic Western concepts that excludes avenues for them to access holistic practices grounded in their culture. Our scoping review explored strategies, approaches, and ways health and wellness can be enhanced by, for, and with Indigenous youth in Canada by identifying barriers/roadblocks and facilitators/strengths to enhancing wellness among Indigenous youth in Canada.

Methods

We applied a systematic approach to searching and critically reviewing peer-reviewed literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews [PRISMA-ScR] as a reporting guideline. Our search strategy focused on specific keywords and MeSH terms for three major areas: Indigenous youth, health, and Canada. We used these keywords, to systematically search the following electronic databases published in English between January 01, 2017, to May 22, 2021: Medline [Ovid], PubMed, ERIC, Web of Science, Scopus, and iportal. We also used hand-searching and snowballing methods to identify relevant articles. Data collected were analysed for contents and themes.

Results

From an initial 1695 articles collated, 20 articles met inclusion criteria for this review. Key facilitators/strengths to enhancing health and wellness by, for, and with Indigenous youth that emerged from our review included: promoting culturally appropriate interventions to engage Indigenous youth; using strength-based approaches; reliance on the wisdom of community Elders; taking responsibility; and providing access to wellness supports. Key barriers/roadblocks included: lack of community support for wellness promotion activities among Indigenous youth; structural/organizational issues within Indigenous communities; discrimination and social exclusion; cultural illiteracy among youth; cultural discordance with mainstream health systems and services; and addictions and risky behaviours.

Conclusion

This scoping review extracted 20 relevant articles about ways to engage Indigenous youth in health and wellness enhancement. Our findings demonstrate the importance of promoting health by, and with Indigenous youth, by engaging them in activities reflexive of their cultural norms, rather than imposing control measures that are incompatible with their value systems.
Cannabidiol use and perceptions in France: a national survey
Authors: Casanova Clémence , Ramier Clémence , Fortin Davide , Carrieri Patrizia , Mancini Julien , Barré Tangui
Published: August 2022

Background

Cannabidiol (CBD), a safe, non-intoxicating cannabis component, is growing in popularity in Europe and worldwide. However, CBD EU regulation is blurry, and consequent labelling and product quality issues may have implications for public health. There is therefore a need to assess the prevalence and perceived harmfulness of CBD use in EU countries, as well as to characterise CBD users. We aimed to do so in the French population.

Methods

In December 2021, an online survey was conducted in a sample respecting the French adult population structure for key demographic variables. Sociodemographic, behavioural and CBD perception data were collected. Three separate regressions were performed to identify correlates of i) having heard of CBD, ii) using CBD, iii) perceived harmfulness of CBD. A hierarchical classification was also performed to identify profiles of CBD users.

Results

The study sample comprised 1969 adults, of whom 69.2% had heard of CBD and 10.1% used it. Less than half (46.8%) of the former considered it harmful. Having heard of CBD was associated with younger age, being born in France, tobacco use, and cannabis use. CBD use was associated with younger age, tobacco use, cannabis use, poor self-reported general health status, and positive perception of alternative medicines. Cluster analysis revealed four different CBD user profiles based on socio-demographics and behavioural characteristics.

Conclusion

Ten percent of the adults in this French study used CBD, and several user profiles emerged. Our results indirectly advocate clearer European CBD regulations to ensure safe and high-quality products.
Chondral delamination of the knee and its management: a case report and review article
Authors: Mansour Marah , Abboud Yazan , Alhaffar Mhd Alaa Aldin , Souliman Ola , Haffar Massa , Mustafa Younes , Alsuliman Tamim , Samaan Michel
Published: August 2022

Chondral delamination is the separation or debonding of the articular cartilage from the underlying subchondral bone. The hyaline cartilage has a limited capacity for healing, meaning it does not possess the innate ability to restore its normal structure or to heal the subchondral bone once detached from it. The purpose of this article is to report the outcomes of a microfracture technique used to manage chondral delamination in a 59-year-old male; we also reviewed the treatment options mentioned in the literature. The patient was admitted to the Department of Orthopedic Surgery complaining of recurrent severe right knee pain with multiple episodes of knee locking, denying any direct or twisting trauma to the knee. The plain X-ray showed mild degenerative changes with articular surface irregularity. On Magnetic resonance imaging, wide chondral delamination was noted in the medial femoral condyle. After 12 months’ post-op, his condition improved. No locking was observed. Pain improved in comparison to the pre-operative levels. The international knee documentation committee improved from 26.4% to 52.9%. In a follow-up magnetic resonance imaging, the adhesion of most parts of the delaminated cartilage.
Estradiol and intrauterine device treatment for moderate and severe intrauterine adhesions after transcervical resection
Authors: Sun Yun , Chen Xiuying , Qian Zhida , Cao Lili , Zhan Sifeng , Huang Lili
Published: August 2022

Objective

To explore the effect of 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) in patients with moderate and severe intrauterine adhesion (IUA) after transcervical resection of adhesion (TCRA).

Methods

Patients with moderate or severe IUA who reived 4 mg/day, 6 mg/day, and 8 mg/day estradiol alone or in combination with an intrauterine device (IUD) after TCRA in Women’s Hospital, Zhejiang University School of Medicine, from March 2014 to December 2014 were enrolled in this retrospective case–control study. In group A, 14 patients received estradiol 4 mg/day + IUD after the first operation; in group B, 29 patients (group B0) received estradiol 6 mg/day after the first operation, and 73 patients (group B1) received estradiol 6 mg/day + IUD; in group C, 14 patients received estradiol 8 mg/day + IUD after the first operation. Referring to ESGE's IUA diagnostic classification method, 72 patients had moderate adhesion, and 58 cases had severe adhesion. Outpatient follow-up was performed at 1 and 23 months and after 1 year. The postoperative menstrual improvement, uterine cavity recovery, drug side effects at two to three months, and pregnancy situation at one year were recorded.

Results

There were no significant differences in age, BMI, and previous intrauterine operation times between the 3 groups (all p > 0.05). Compared with Group A, more patients in group C had severe IUA (p = 0.008). In addition, there were no differences in menstrual recovery, uterine cavity recovery, and pregnancy in one year between the 3 groups (p > 0.05) and between groups B0 and B1 (p > 0.05). In group B1, 51 (69.86%) patients had IUD incarceration.

Conclusion

This data suggests that 4 mg/d doses of estrogen may have the same effect in improving the menstrual condition, uterine cavity morphology, and reproductive ability compared to a higher dosage (6 mg/day estrogen and 8 mg/day). In addition, the placement of IUD in the uterine cavity during TCRA may cause IUD incarceration, and the treatment results for the prevention of IUA are not better than without IUD.
On the analysis of data augmentation methods for spectral imaged based heart sound classification using convolutional neural networks
Authors: Zhou George , Chen Yunchan , Chien Candace
Published: August 2022

Background

The application of machine learning to cardiac auscultation has the potential to improve the accuracy and efficiency of both routine and point-of-care screenings. The use of convolutional neural networks (CNN) on heart sound spectrograms in particular has defined state-of-the-art performance. However, the relative paucity of patient data remains a significant barrier to creating models that can adapt to a wide range of potential variability. To that end, we examined a CNN model’s performance on automated heart sound classification, before and after various forms of data augmentation, and aimed to identify the most optimal augmentation methods for cardiac spectrogram analysis.

Results

We built a standard CNN model to classify cardiac sound recordings as either normal or abnormal. The baseline control model achieved a PR AUC of 0.763 ± 0.047. Among the single data augmentation techniques explored, horizontal flipping of the spectrogram image improved the model performance the most, with a PR AUC of 0.819 ± 0.044. Principal component analysis color augmentation (PCA) and perturbations of saturation-value (SV) of the hue-saturation-value (HSV) color scale achieved a PR AUC of 0.779 ± 045 and 0.784 ± 0.037, respectively. Time and frequency masking resulted in a PR AUC of 0.772 ± 0.050. Pitch shifting, time stretching and compressing, noise injection, vertical flipping, and applying random color filters negatively impacted model performance. Concatenating the best performing data augmentation technique (horizontal flip) with PCA and SV perturbations improved model performance.

Conclusion

Data augmentation can improve classification accuracy by expanding and diversifying the dataset, which protects against overfitting to random variance. However, data augmentation is necessarily domain specific. For example, methods like noise injection have found success in other areas of automated sound classification, but in the context of cardiac sound analysis, noise injection can mimic the presence of murmurs and worsen model performance. Thus, care should be taken to ensure clinically appropriate forms of data augmentation to avoid negatively impacting model performance.
Cellular transcriptional alterations of peripheral blood in Alzheimer’s disease
Authors: Song Liting , Yang Yucheng T. , Guo Qihao ,   the ZIB Consortium, Zhao Xing-Ming
Published: August 2022

Background

Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the most common cause of dementia worldwide. Accumulating data support the contributions of the peripheral immune system in AD pathogenesis. However, there is a lack of comprehensive understanding about the molecular characteristics of peripheral immune cells in AD.

Methods

To explore the alterations of cellular composition and the alterations of intrinsic expression of individual cell types in peripheral blood, we performed cellular deconvolution in a large-scale bulk blood expression cohort and identified cell-intrinsic differentially expressed genes in individual cell types with adjusting for cellular proportion.

Results

We detected a significant increase and decrease in the proportion of neutrophils and B lymphocytes in AD blood, respectively, which had a robust replicability across other three AD cohorts, as well as using alternative algorithms. The differentially expressed genes in AD neutrophils were enriched for some AD-associated pathways, such as ATP metabolic process and mitochondrion organization. We also found a significant enrichment of protein-protein interaction network modules of leukocyte cell-cell activation, mitochondrion organization, and cytokine-mediated signaling pathway in neutrophils for AD risk genes includingCD33andIL1B. Both changes in cellular composition and expression levels of specific genes were significantly associated with the clinical and pathological alterations. A similar pattern of perturbations on the cellular proportion and gene expression levels of neutrophils could be also observed in mild cognitive impairment (MCI). Moreover, we noticed an elevation of neutrophil abundance in the AD brains.

Conclusions

We revealed the landscape of molecular perturbations at the cellular level for AD. These alterations highlight the putative roles of neutrophils in AD pathobiology.
Low mitochondrial DNA copy number induces chemotherapy resistance via epithelial-mesenchymal transition by DNA methylation in esophageal squamous cancer cells
Authors: Kubo Yuto , Tanaka Koji , Masuike Yasunori , Takahashi Tsuyoshi , Yamashita Kotaro , Makino Tomoki , Saito Takuro , Yamamoto Kazuyoshi , Tsujimoto Tomoyuki , Harino Takashi , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Eguchi Hidetoshi , Doki Yuichiro
Published: August 2022

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most severe cancers and is characterized by chemotherapy resistance and poor prognosis associated with epithelial-mesenchymal transition (EMT). In a previous study, a low mitochondrial DNA (mtDNA) copy number was associated with poorer prognosis and induced EMT in ESCC. However, the detailed mechanism related to mtDNA copy number and EMT is unclear. The aim of this study was to clarify the mechanism by which a change in mtDNA copy number contributes to EMT and to examine treatment of chemotherapy resistance in ESCC.

Methods

The association between low mtDNA copy number and chemotherapy resistance was investigated using specimens from 88 patients who underwent surgery after neoadjuvant chemotherapy. Then, the mtDNA content of human ESCC cell lines, TE8 and TE11, was depleted by knockdown of mitochondrial transcription factor A expression. The present study focused on modulation of mitochondrial membrane potential (MMP) and DNA methylation as the mechanisms by which mtDNA copy number affects EMT. mRNA and protein expression, chemotherapy sensitivity, proliferation, MMP and DNA methylation were evaluated, and in vitro and in vivo assays were conducted to clarify these mechanisms.

Results

ESCC patients with decreased mtDNA copy number who underwent R0 resection after neoadjuvant chemotherapy had significantly worse pathological response and recurrence-free survival. Additionally, low mtDNA copy number was associated with resistance to chemotherapy in vitro and in vivo. mtDNA controlled MMP, and MMP depolarization induced EMT. Depletion of mtDNA and low MMP induced DNA methylation via a DNA methylation transcription factor (DNMT), and a DNMT inhibitor suppressed EMT and improved chemotherapy sensitivity in mtDNA-depleted ESCC cells, as shown by in vitro and in vivo assays.

Conclusion

This study showed that decreased mtDNA copy number induced EMT via modulation of MMP and DNA methylation in ESCC. Therapeutic strategies increasing mtDNA copy number and DNMT inhibitors may be effective in preventing EMT and chemosensitivity resistance.
Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study
Authors: Liu Shu-Ying , Qiao Hong-Wen , Song Tian-Bin , Liu Xiu-Lin , Yao Yun-Xia , Zhao Chun-Song , Barret Olivier , Xu Sheng-Li , Cai Yan-Ning , Tamagnan Gilles D. , Sossi Vesna , Lu Jie , Chan Piu
Published: August 2022

Background

Abnormal activation of immune system is an important pathogenesis of Parkinson’s disease, but the relationship between peripheral inflammation, central microglia activation and dopaminergic degeneration remains unclear.

Objectives

To evaluate the brain regional microglia activation and its relationship with clinical severity, dopaminergic presynaptic function, and peripheral inflammatory biomarkers related to adaptive immunity.

Methods

In this case–control study, we recruited 23 healthy participants and 24 participants with early-stage Parkinson’s disease. 18F-PBR06 PET/MR for microglia activation, 18F-FP-DTBZ for dopaminergic denervation, total account of T cells and subpopulations of T helper (Th1/Th2/Th17) cells, and the levels of serum inflammatory cytokines were assessed. Sanger sequencing was used to exclude the mix-affinity binders of 18F-PBR06-PET.

Results

Compared to healthy controls, patients with Parkinson’s disease had an increased 18F-PBR06-PET standardized uptake value ratio (SUVR) in the putamen, particularly in the ipsilateral side of the motor onset. 18F-PBR06-PET SUVR was positively associated with 18F-FP-DTBZ-PET SUVR in the brainstem and not associated with disease severity measured by Hoehn and Yahr stage, MDS-UPDRS III scores. Patients with Parkinson’s disease had elevated frequencies of Th1 cells and serum levels of IL10 and IL17A as compared to healthy controls. No significant association between peripheral inflammation markers and microglia activation in the brain of PD was observed.

Conclusion

Parkinson’s disease is associated with early putaminal microglial activation and peripheral phenotypic Th1 bias. Peripheral adaptive immunity might be involved in microglia activation in the process of neurodegeneration in PD indirectly, which may be a potential biomarker for the early detection and the target for immunomodulating therapy.
The uniportal VATS in the treatment of stage II pleural empyema: a safe and effective approach for adults and elderly patients—a single-center experience and literature review
Authors: Luciani Claudio , Scacchi Andrea , Vaschetti Roberto , Di Marzo Giancarlo , Fatica Ilaria , Cappuccio Micaela , Guerra Germano , Ceccarelli Graziano , Avella Pasquale , Rocca Aldo
Published: August 2022

Background

Pleural empyema (PE) is a frequent disease, associated with a high morbidity and mortality. Surgical approach is the standard of care for most patients with II-III stage PE. In the last years, the minimally invasive surgical revolution involved also thoracic surgery allowing the same outcomes in terms of safety and effectiveness combined to better pain management and early discharge. The aim of this study is to demonstrate through our experience on uniportal-video-assisted thoracoscopy (u-VATS) the effectiveness and safety of its approach in treatment of stage II PE. As secondary endpoint, we will evaluate the different pattern of indication of u-VATS in adult and elderly patients with literature review.

Methods

We retrospectively reviewed our prospectively collected database of u-VATS procedures from November 2018 to February 2022, in our regional referral center for Thoracic Surgery of Regione Molise General Surgery Unit of “A. Cardarelli” Hospital, in Campobasso, Molise, Italy.

Results

A total of 29 patients underwent u-VATS for II stage PE. Fifteen (51.72%) patients were younger than 70 years old, identified as “adults,” 14 (48.28%) patients were older than 70 years old, identified as “elderly.” No mortality was found. Mean operative time was 104.68 ± 39.01 min in the total population. The elderly group showed a longer operative time (115 ± 53.15 min) (p = 0.369). Chest tube was removed earlier in adults than in elderly group (5.56 ± 2.06 vs. 10.14 ± 5.58 p = 0.038). The Length of Stay (LOS) was shorter in the adults group (6.44 ± 2.35 vs. 12.29 ± 6.96 p = 0.033). Patients evaluated through Instrumental Activities of Daily Living (IADL) scale returned to normal activities of daily living after surgery.

Conclusion

In addition, the u-VATS approach seems to be safe and effective ensuring a risk reduction of progression to stage III PE with a lower recurrence risk and septic complications also in elderly patients. Further comparative multicenter analysis are advocated to set the role of u-VATS approach in the treatment of PE in adults and elderly patients.
Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial
Authors: Dianti Jose , Fard Samira , Wong Jenna , Chan Timothy C. Y. , Del Sorbo Lorenzo , Fan Eddy , Amato Marcelo B. Passos , Granton John , Burry Lisa , Reid W. Darlene , Zhang Binghao , Ratano Damian , Keshavjee Shaf , Slutsky Arthur S. , Brochard Laurent J. , Ferguson Niall D. , Goligher Ewan C.
Published: August 2022

Background

Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing − 3 to − 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF.

Methods

In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort.

Results

Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets.

Conclusion

Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy.

Trial registration: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).
Comparison of weight loss induced by daily caloric restriction versus intermittent fasting (DRIFT) in individuals with obesity: study protocol for a 52-week randomized clinical trial
Authors: Ostendorf Danielle M. , Caldwell Ann E. , Zaman Adnin , Pan Zhaoxing , Bing Kristen , Wayland Liza T. , Creasy Seth A. , Bessesen Daniel H. , MacLean Paul , Melanson Edward L. , Catenacci Victoria A.
Published: August 2022

Background

The standard of care for treating overweight and obesity is daily caloric restriction (DCR). While this approach produces modest weight loss, adherence to DCR declines over time and weight regain is common. Intermittent fasting (IMF) is an alternative dietary strategy for reducing energy intake (EI) that involves >60% energy restriction on 2–3 days per week, or on alternate days, with habitual intake on fed days. While numerous studies have evaluated IMF as a weight loss strategy, there are several limitations including lack of a standard-of-care DCR control, failure to provide guideline-based behavioral support, and failure to rigorously evaluate dietary and PA adherence using objective measures. To date, only three longer-term (52-week) trials have evaluated IMF as a weight loss strategy. None of these longer-duration studies reported significant differences between IMF and DCR in changes in weight. However, each of these studies has limitations that prohibit drawing generalizable conclusions about the relative long-term efficacy of IMF vs. DCR for obesity treatment.

Methods

The Daily Caloric Restriction vs. Intermittent Fasting Trial (DRIFT) is a two-arm, 52-week block randomized (1:1) clinical weight loss trial. The two intervention arms (DCR and IMF) are designed to prescribe an equivalent average weekly energy deficit from baseline weight maintenance energy requirements. Both DCR and IMF will be provided guideline-based behavioral support and a PA prescription. The primary outcome is change in body weight at 52 weeks. Secondary outcomes include changes in body composition (dual-energy x-ray absorptiometry (DXA)), metabolic parameters, total daily energy expenditure (TDEE, doubly labeled water (DLW)), EI (DLW intake-balance method, 7-day diet diaries), and patterns of physical activity (PA, activPAL device).

Discussion

Although DCR leads to modest weight loss success in the short-term, there is wide inter-individual variability in weight loss and poor long-term weight loss maintenance. Evidence-based dietary approaches to energy restriction that are effective long-term are needed to provide a range of evidence-based options to individuals seeking weight loss. The DRIFT study will evaluate the long-term effectiveness of IMF vs. DCR on changes in objectively measured weight, EI, and PA, when these approaches are delivered using guideline-based behavioral support and PA prescriptions.
Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial
Authors: Fankhauser Christian D. , Affentranger Andres , Cortonesi Beatrice , Jeker Urs , Gass Markus , Minervini Fabrizio , Jung Georg , Christmann Corina , Brambs Christine , Puhan Milo A. , Held Ulrike
Published: August 2022

Background

At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery.

Methods

The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption.

Discussion

The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery.

Trial registration

BASEC #2021-02004; ClinicalTrials.gov: NCT05192837. Registered on January 14, 2022.
Rhodnius (Stål, 1859) (Hemiptera, Triatominae) genus in Bolivian Amazonia: a risk for human populations?
Authors: Depickère Stéphanie , Villacís Anita G. , Santillán-Guayasamín Soledad , Callapa Rafael Jorgia Esperanza , Brenière Simone Frédérique , Revollo Zepita Susana
Published: August 2022

Background

Chagas disease, one of the most important neglected tropical diseases in the countries of Latin America, is considered to be a particularly important public health concern in the Amazon region due to increases in the number of outbreaks of acute Chagas disease and increased local transmission in the last 20 years. However, relative to other countries, in Bolivia there is little information available on its transmission in the Amazon region. The aim of this study was to investigate the infestation of palm trees, the main habitat of Triatominae in the region, in several localities, to evaluate the danger they represent to inhabitants.

Methods

Triatominae were collected using live bait traps left overnight in six localities in Pando and Beni Departments, Bolivia. DNA extraction and sequencing were used to establish the Triatominae species (Cytb, 16S and 28S-D2 gene fragments), and the blood meal sources (Cytb fragment). Trypanosoma sp. infection was analyzed by sequencing gene fragments (GPX, GPI, HMCOAR, LAP, PDH and COII) or by mini-exon multiplex PCR.

Results

A total of 325 Rhodnius were captured (97.3% of nymphs) from the 1200 traps placed in 238 palm trees and 32 burrows/ground holes. Sequence analyses on DNA extracted from 114 insects and phylogeny analysis identified two triatomine species: Rhodnius stali (17%) and Rhodnius montenegrensis (equated to Rhodnius robustus II, 83%). These were found in palm trees of the genera Attalea (69%), Astrocaryum (13%), Copernicia (12%), Euterpe (2%) and Acrocomia (1%). The infection rate was around 30% (165 analyzed insects), with 90% of analyzed insects infected by Trypanosoma cruzi (only the TcI discrete typing unit was detected), 3% infected by Trypanosoma rangeli (first time found in Bolivian Triatominae) and 7% infected by mixed T. cruzi (TcI)-T. rangeli. Rhodnius specimens fed on Didelphidae, rodents, gecko and humans.

Conclusions

The results of this study highlight the epidemiological importance of Rhodnius in the Bolivian Amazon region. The huge geographical distribution of Rhodnius and their proximity to the human dwellings, high infection rate and frequent meals on the human population highlight a risk of transmission of Chagas disease in the region.

Graphical Abstract