bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported outcome (PRO) results from the AGITG DOCTOR trial: a randomised phase 2 trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma
Authors: Mercieca-Bebber R. , Barnes E. H. , Wilson K. , Samoon Z. , Walpole E. , Mai T. , Ackland S. , Burge M. , Dickie G. , Watson D. , Leung J. , Wang T. , Bohmer R. , Cameron D. , Simes J. , Gebski V. , Smithers M. , Thomas J. , Zalcberg J. , Barbour A. P.
Published: March 2022

Background

AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years.

Methods

Participants (N = 116) completed the EORTC QLQ-C30 and oesophageal module (QLQ-OES18) before chemotherapy (baseline), before surgery, six and 12 weeks post-surgery and three-monthly until 2 years. We plotted PROs over time and calculated the percentage of participants per treatment group whose post-surgery score was within 10 points (threshold for clinically relevant change) of their baseline score, for each PRO scale. We examined the relationship between Grade 3+ adverse events (AEs) and PROs. This analysis included four groups: CF responders, non-responders randomised to DCF, non-responders randomised to DCF + RT, and “others” who were not randomised.

Results

Global QOL was clinically similar between groups from 6 weeks post-surgery. All groups had poorer functional and higher symptom scores during active treatment and shortly after surgery, particularly the DCF and DCF + RT groups. DCF + RT reported a clinically significant difference (−13points) in mean overall health/QOL between baseline and pre-surgery. Similar proportions of patients across groups scored +/− 10 points of baseline scores within 2 years for most PRO domains. Instance of grade 3+ AEs were not related to PROs at baseline or 2 years.

Conclusions

By 2 years, similar proportions of patients scored within 10 points of baseline for most PRO domains, with the exception of pain and insomnia for the DCF + RT group. Non-responders randomised to DCF or DCF + RT experienced additional short-term burden compared to CF responders, reflecting the longer duration of neoadjuvant treatment and additional toxicity. This should be weighed against clinical benefits reported in AGITG DOCTOR. This data will inform communication of the trajectory of treatment options for early CF non-responders.

Trial registration

Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12609000665235. Registered 31 July 2009.
Serum exosomal proteomics analysis of lung adenocarcinoma to discover new tumor markers
Authors: Liu Shanshan , Tian Wenjuan , Ma Yuefeng , Li Jiaji , Yang Jun , Li Burong
Published: March 2022

Background

Among the most aggressive and rapidly lethal types of lung cancer, lung adenocarcinoma is the most common type. Exosomes, as a hot area, play an influential role in cancer. By using proteomics analysis, we aimed to identify potential markers of lung adenocarcinoma in serum.

Methods

In our study, we used the ultracentrifugation method to isolate serum exosomes. The Liquid chromatography-mass spectrometry (LC–MS) and bioinformatics analysis were used to identify potential serum exosomal proteins with altered expression among patients with advanced lung adenocarcinoma, early lung adenocarcinoma, and healthy controls. A western blot (WB) was performed to confirm the above differential expression levels in a separate serum sample-isolated exosome, and immunohistochemistry (IHC) staining was conducted to detect expression levels of the above differential proteins of serum exosomes in lung adenocarcinoma tissues and adjacent tissues. Furthermore, we compared different expression models of the above differential proteins in serum and exosomes.

Result

According to the ITGAM (Integrin alpha M chain) and CLU (Clusterin) were differentially expressed in serum exosomes among different groups as well as tumor tissues and adjacent tissues. ITGAM was significantly and specifically enriched in exosomes. As compared to serum, CLU did not appear to be significantly enriched in exosomes. ITGAM and CLU were identified as serum exosomal protein markers of lung adenocarcinoma.

Conclusions

This study can provide novel ideas and a research basis for targeting lung adenocarcinoma treatment as a preliminary study.
Prevalence and correlates of suicide attempts in high-risk populations: a cross-sectional study among patients receiving opioid agonist therapy in Norway
Authors: Vold Jørn Henrik , Løberg Else-Marie , Aas Christer F. , Steier Jan Alexander , Johansson Kjell Arne , Fadnes Lars Thore
Published: March 2022

Background

Death by suicide in patients enrolled in opioid agonist therapy (OAT) is a major clinical concern. However, little knowledge exists regarding suicide attempts in this patient group. This study presents the lifetime prevalence of suicide attempts and the associations between suicide attempts and clinical and sociodemographic variables such as education, sex, early onset of substance use (< 13 years of age), substance use patterns, and injecting substance use among patients receiving OAT.

Methods

We used data from a cohort of OAT patients in Norway obtained from a health assessment of self-reported suicide attempts and sociodemographic and clinical factors. A total of 595 patients receiving OAT were assessed from 2016 to 2020. A binary logistic regression analysis was performed and reported with an unadjusted odds ratio and 95% confidence intervals (OR). The purpose of this assessment was to analyze associations between suicide attempts and substance use patterns as well as the injection of substances during the 30 days leading up to the health assessment. A negative binomial regression analysis with an incidence rate ratio and 95% confidence intervals (IRR) was performed to investigate sex, education, early onset of substance use, and the number of suicide attempts.

Results

Forty-one percent of the OAT patients had attempted to die by suicide at least once during their lifetime. An early onset of substance use was strongly associated with the suicide attempts (IRR: 1.7, 1.3–2.2). No significant association was found between suicide attempts and sex (IRR: 1.2, 0.9–1.6) or education (IRR: 0.6, 0.2–2.1). Likewise, no association was identified between suicide attempts and injecting substance use (OR: 0.9, 0.6–1.3), nor using alcohol (OR: 0.9, 0.7–1.3), amphetamines (OR: 1.0, 0.7–1.3), benzodiazepines (OR: 1.0, 0.7–1.4), cannabis (OR: 1.2, 0.9–1.7), cocaine (OR: 1.3, 0.6–3.0), or opioids (OR: 1.4, 0.9–2.0).

Conclusion

The lifetime prevalence of suicide attempts was alarmingly high in the OAT population. An early onset of substance use seemed to be an important risk factor for suicide attempts. There was a non-significant association to more current use of opioids among OAT patients with previous suicide attempts.
Respiratory MUC5B disproportion is involved in severe community-acquired pneumonia
Authors: Fan Lu , Lu Yi , Wang Yan , Zhang Xiaomin , Wu Yuxuan , Sun Hao , Zhang Jinsong
Published: March 2022

Background

Mucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity.

Methods

A total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity.

Results

MUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92–25.79) vs. SCAP 8.20 µg/ml (IQR 4.97–14.03), p = 0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15–1.10) vs. SCAP 0.68 mg/ml (IQR 0.46–1.69), p = 0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50–5.56%) vs. SCAP 1.38% (IQR 0.73–1.76%), p < 0.001]. MUC5B/total protein ratio was negatively correlated with total protein concentration (rs = − 0.576, p < 0.001), IL6 (rs = − 0.312, p = 0.001), IL10 (rs = − 0.228, p = 0.013), IL13 (rs = − 0.183, p = 0.048), IL17 (rs = − 0.282, p = 0.002) and CURB-65 score (rs = − 0.239, p = 0.009). Logistic regression identified that MUC5B/total protein ratio, IL6 level and CURB-65 score as independent variables related to CAP severity. ROC curve demonstrated best assessment value of MUC5B/total protein ratio for SCAP (AUC 0.803, p < 0.001), with a sensitivity of 88.9% and a specificity of 64.4%.

Conclusions

Respiratory MUC5B disproportion is related to CAP severity. MUC5B/total protein ratio may serve as an assessment marker and a potential therapeutic target for severe CAP.
Dexmedetomidine versus propofol sedation in flexible bronchoscopy: a randomized controlled trial
Authors: Pertzov Barak , Krasulya Boris , Azem Karam , Shostak Yael , Izhakian Shimon , Rosengarten Dror , kharchenko Svetlana , Kramer Mordechai R.
Published: March 2022

Background

Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes.

Methods

We conducted an RCT to evaluate the efficacy and safety of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was the number of desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction.

Results

Overall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0–1) and 1 (0–2) in the DEX and control groups, respectively (P = 0.29). Median desaturation time was 1 (0–2) and 1 (0–3) minutes in the DEX and control groups, respectively (P = 0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P = 0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P = 0.009).

Conclusion

Dexmedetomidine sedation during bronchoscopy did not show differences in oxygen saturation and transcutaneous CO2 level in comparison to propofol. Moreover, DEX sedation required a significantly higher number of rescue boluses, due to inadequate sedation and was associated with a higher rate of adverse events.

Trial registration NCT04211298, registration date: 26.12.2019.
Spinopelvic alignment and low back pain after total hip arthroplasty: a scoping review
Authors: Pourahmadi Mohammadreza , Sahebalam Mohammad , Dommerholt Jan , Delavari Somayeh , Mohseni-Bandpei Mohammad Ali , Keshtkar Abbasali , Fernández-de-Las-Peñas César , Mansournia Mohammad Ali
Published: March 2022

Objective

Spinopelvic alignment is increasingly considered as an essential factor for maintaining an energy-efficient posture in individuals with normal or pathological status. Although several previous studies have shown that changes in the sagittal spinopelvic alignment may occur in patients undergoing total hip arthroplasty (THA), no review of this area has been completed so far. Thus, the objective of this scoping review was to summarize the evidence investigating changes in spinopelvic alignment and low back pain (LBP) following THA.

Data sources

We adhered to the established methodology for scoping reviews. Four electronic databases were systematically searched from inception-December 31, 2021.

Study selection

We selected prospective or retrospective observational or intervention studies that included patients with THA.

Data extraction

Data extraction and levels of evidence were independently performed using standardized checklists.

Data synthesis

A total of 45 papers were included in this scoping review, involving 5185 participants with THA. Pelvic tilt was the most common parameter measured in the eligible studies (n = 26). The results were not consistent across all studies; however, it was demonstrated that the distribution of pelvic tilt following THA had a range of 25° posterior to 20° anterior. Moreover, decreased sacral slope and lower pelvic incidence were associated with increased risk of dislocation in patients with THA. Lumbar spine scoliosis did not change significantly after THA in patients with bilateral hip osteoarthritis (5.50°(1.16°) vs. 3.73°(1.16°); P-value = 0.29). Finally, one study indicated that LBP improvement was not correlated with postoperative changes in spinopelvic alignment parameters. Several methodological issues were addressed in this study, including no sample size calculation and no type-I error adjustment for outcome multiplicity.

Conclusions

Changes in spinopelvic alignment may occur after THA and may improve with time. Patients with a THA dislocation usually show abnormal spinopelvic alignment compared to patients without a THA dislocation. LBP usually improves markedly over time following THA.
Evaluation of anticandidal activities and phytochemical examination of extracts prepared from Vitex agnus-castus: a possible alternative in treating candidiasis infections
Authors: Al-Otibi Fatima O. , Alrumaizan Ghaida I. , Alharbi Raedah I.
Published: March 2022

Background

Candidiasis infection is associated with high morbidity and mortality. Fungicidal resistance of some commercially used fungicides ascended the need for a naturally effective alternative. The current study aimed to evaluate the fungicidal activity of Vitex agnus-castus extracts in vitro against some Candida species.

Methods

The bioactive compounds contained in the crude and alcoholic extracts were compared, and the antioxidant activity was tested, as well. The phytochemical analysis was carried out by Fourier Transform-Infrared Spectroscopy (FTIR) and Gas Chromatography-Mass Spectrometry (GC/MS). The scavenger activity of the tested extracts was tested, as well. The anticandidal activity was tested to detect the effect of the tested extracts on the mycelial growth of Candida albicans, Candida krusei, Candida parapsilosis, Candia tropicalis, Candida famata, Candida rhodotorula, and Candida dublinesis. The minimum inhibitory concentrations were calculated for all reported activities. The Scanning Electron Microscopy (SEM) and the Transmission Electron Microscopy (TEM) were used to detect the morphological and ultrastructure response in some selected species.

Results

FTIR and GC/MS revealed the existence of different bioactive chemical groups such as polyphenols, fatty acids, terpenes, terpenoids, steroids, aldehydes, alcohols, and esters, phytol which is a diterpene. DPPH results confirmed the antioxidant activity of all extracts where the methanolic extract was the strongest scavenging substrate. All extracts showed strong inhibitory effects against different species at a concentration of 200 µg/ml (P < 0.001). SEM and TEM showed morphological and ultrastructure changes in C. famata.

Conclusion

The current study suggested a reliable antifungal activity of different extracts of Vitex agnus-castus against different Candida species and strains. However, further studies are required to confirm the safety of these extracts to be used in medical applications.
Traditional and complementary medicine use among cancer patients in Nepal: a cross-sectional survey
Authors: Choi Soo Jeung , Kunwor Sangita Karki , Im Hyea Bin , Hwang Jung Hye , Choi Dain , Han Dongwoon
Published: March 2022

Background

Traditional and complementary medicine (T&CM) is commonly used in South Asian countries such as Nepal. There are various causes and contributing factors for patients with cancer to consider using T&CM. However, little is known about the use of T&CM among the cancer population in this region.

Methods

The study followed a cross-sectional design using a structured survey questionnaire. Survey participants were recruited from two National hospitals in Kathmandu, Nepal. The survey instrument comprised 30 questions, including variables on demographics, use of T&CM, and perceived level of disease severity, and cancer treatment. Chi-square test and logistic regression were used for data analysis using SPSS ver. 23.0.

Results

Of 908 participants, 31.6% used one or more modalities of T&CM after a cancer diagnosis. The most commonly used T&CM was Ayurveda (46.5%), followed by yoga (32.4%). About 46% of T&CM users discussed their use with their doctors. The main source of information on T&CM was their family members and relatives (55.7%). Cancer type (head and neck cancer OR: 2.30, CI: 1.23–4.29; abdominal cancer OR: 2.69, CI: 1.47–4.95; lung cancer OR: 5.88, CI: 2.69–12.89), cancer stage (Stage I OR: 1.92¸CI: 1.14–3.25; Stage II OR: 1.76, CI: 1.06–2.94), and the patients’ self-rated disease severity (high perceived severity OR: 1.50, CI: 1.05–2.16) were strong predictors of T&CM use.

Conclusion

This study underlined that despite the widespread use of T&CM among cancer patients in Nepal, most patients obtained information on T&CM from informal sources and did not disclose their use to physicians. To ensure the safe use of T&CM modalities, physicians should integrate questions on T&CM use into routine patient assessments in order to facilitate active communication and improve the quality of care.
Acceptability and feasibility of HIV recent infection surveillance by healthcare workers using a rapid test for recent infection at HIV testing sites — Malawi, 2019
Authors: Arons Melissa M. , Curran Kathryn G. , Msukwa Malango , Theu Joe , O’Malley Gabrielle , Ernst Alexandra , Namakhoma Ireen , Bello George , Telford Carson , Shanmugam Vedapuri , Parekh Bharat , Kim Evelyn , Dobbs Trudy , Payne Danielle , Gugsa Salem
Published: March 2022

Background

The Malawi Ministry of Health implemented a new surveillance activity in April 2019 to detect recent HIV infections using a rapid test for recent infection (RTRI) to identify areas of ongoing transmission and guide response activities.

Setting

At 23 health facilities in Blantyre District, healthcare workers (HCWs) were trained to conduct recent infection testing. In September 2019, we conducted a cross-sectional survey at these sites to explore the acceptability and feasibility of integrating this activity into routine HIV testing services (HTS).

Methods

Research assistants interviewed HCWs using a semi-structured survey. Descriptive statistics were used to summarize quantitative responses and thematic analysis was used to group open-ended text.

Results

We interviewed 119 HCWs. Eighty-two percent of participants reported the RTRI was easy-to-use. HCWs perceived high client acceptability; 100% reported clients as ‘somewhat’ or ‘very accepting’. Challenges included 68% of HCWs estimating they spend ≥20 min beyond routine HTS per client for this activity and 51% performing at least two additional finger pricks to complete the testing algorithm. HCWs differed in their perceptions of whether results should be returned to clients.

Conclusion

This study assessed HCW experiences using point-of-care RTRIs for HIV recent infection surveillance. Overall, HCWs perceived RTRIs to be acceptable, easy-to-use, and valuable. Though only clients with new HIV diagnoses are tested for recent infection, additional time may be substantial at high-volume health service delivery points. Providing response plans or aggregated recent infection results to HCWs and/or clients may support motivation and sustainability of this novel surveillance activity.
“The real pandemic’s been there forever”: qualitative perspectives of domestic and family violence workforce in Australia during COVID-19
Authors: Baffsky Rachel , Beek Kristen , Wayland Sarah , Shanthosh Janani , Henry Amanda , Cullen Patricia
Published: March 2022

Background

In 2020, Australia, like most countries, introduced restrictions related to the global pandemic of coronavirus disease 2019 (COVID-19). Frontline services in the domestic and family violence (DFV) sector had to adapt and innovate to continue supporting clients who were experiencing and/or at risk of DFV. There is a need to understand from the perspective of those on the frontline how DFV service responses in different contexts impacted their working conditions and subsequent wellbeing, and what they want to see continued in ‘the new normal’ to inform future effective practices. We address this by reporting on findings from in-depth interviews conducted with practitioners and managers from the DFV sector in Australia.

Methods

Between July and September 2020 semi-structured interviews were conducted with 51 DFV practitioners and managers from a range of services and specialisations across legal, housing, health and social care services. The data was analysed using iterative thematic analysis.

Results

The most common service adaptations reported were shifting to outreach models of care, introducing infection control procedures and adopting telehealth/digital service delivery. Adjacent to these changes, participants described how these adaptations created implementation challenges including increased workload, maintaining quality and safety, and rising costs. Impacts on practitioners were largely attributed to the shift towards remote working with a collision in their work and home life and increased risk of vicarious trauma. Despite these challenges, most expressed a sense of achievement in how their service was responding to COVID-19, with several adaptations that practitioners and managers wanted to see continued in ‘the new normal’, including flexible working and wellbeing initiatives.

Conclusions

The pandemic has amplified existing challenges for those experiencing DFV as well as those working on the frontline of DFV. Our findings point to the diversity in workforce experiences and has elucidated valuable lessons to shape future service delivery. Given the continuing impacts of the pandemic on DFV, this study provides timely insight and impetus to strengthen the implementation of remote working and telehealth/digital support across the DFV sector and to inform better supports for DFV workforce wellbeing in Australia and other contexts.

Trial registration

Not a clinical intervention.
The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance
Authors: Li Tiezhi , Zhang Helin , Wang Zhichao , Gao Shaolin , Zhang Xu , Zhu Haiyong , Wang Na , Li Honglin
Published: March 2022

Background

Autophagy has been found to be involved in the multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC.

Methods

We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC.

Results

H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 μg/ml for 24 h increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples.

Conclusions

The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.
NCAPG facilitates colorectal cancer cell proliferation, migration, invasion and epithelial–mesenchymal transition by activating the Wnt/β-catenin signaling pathway
Authors: Shi Yanlong , Ge Chang , Fang Debao , Wei Wei , Li Li , Wei Qian , Yu Hongzhu
Published: March 2022

Background

The condensation complex gene non-SMC condensin I complex subunit G(NCAPG), a cell cycle-associated condensin, is over-expressed in various cancers. However, its biological function in colorectal cancer (CRC) has yet to be deciphered. In this study, we investigated the role of NCAPG in CRC progression.

Methods

Tissues and cells were used to measure NCAPG expression levels and their association with clinicopathological characteristics. NCAPG silencing and overexpression in CRC cells were used to measure its effect on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) progression. In addition, mRNA, and protein expression levels of key EMT biomarkers were measured. The underlying mechanism of NCAPG modulating CRC progression was further explored using western blotting, co-immunoprecipitation (CO-IP), and immunofluorescence (IF) assays.

Results

NCAPG was over-expressed in CRC tissues and cell lines. High expression levels were associated with differentiation levels, lymph metastasis, and vascular invasion in patients. NCAPG silencing suppressed, while NCAPG overexpression promoted the proliferative, migration, and invasive capacity of HCT116 and SW480 cells. Mechanistically, we discovered that NCAPG participated in regulating the EMT process and the Wnt/β-catenin signaling pathway to facilitate CRC invasion and metastasis. Additional experiments demonstrated that NCAPG activated the Wnt/β-catenin signaling pathway by binding to β-catenin in CRC cells.

Conclusion

NCAPG acts as an oncogene involved in the development and progression of CRC by binding to β-catenin to activate the Wnt/β-catenin signaling pathway.
Why using bed nets is a challenge among minority populations in Central Vietnam
Authors: Nguyen Thuan Thi , Nguyen Xa Xuan , Wilson-Barthes Marta , Sawada Ikumi , Muela Joan , Hausmann-Muela Susanna , Pham Thanh Vinh , Van Nguyen Hong , Van Nguyen Van , Tran Duong Thanh , Gryseels Charlotte , D’Alessandro Umberto , Grietens Koen Peeters , Erhart Annette
Published: March 2022

Background

Despite freely distributed insecticide-treated nets (ITNs) and health information campaigns to increase their use among populations at risk, malaria transmission persists in forested areas in Vietnam, especially among ethnic minority communities. A mixed-methods study was conducted in four villages of Ca Dong and M’nong ethnicity in Central Vietnam between 2009 and 2011 to assess factors limiting the uptake of ITNs.

Methods

The mixed-methods research design consisted of a qualitative study to explore the context and barriers to ITN use, and a cross-sectional household survey (n = 141) to quantify factors for limited and appropriate net use.

Results

The Ca Dong and M’nong’s livelihood was dependent on swidden farming in the forest. Poverty-related factors, including the lack of beds, blankets, the practice of sleeping around the kitchen fire and deteriorated ITNs due to open housing structures, were reasons for alternative and non-use of ITNs. When household members stayed overnight in plot huts at fields, ITNs were even more unavailable and easily deteriorated. 72.5% of households reported having received one net for every two persons, and 82.2% of participants reported to have used ITNs the night before the survey. However, only 18.4% of participants were estimated to be effectively protected by ITNs after accounting for the availability of torn ITNs and the way ITNs were used, for example as blankets, at both village and fields. Multi-variable logistic regression showed the effect of four significant factors for appropriate ITN use: i) being female (AOR = 8.08; p = 0.009); ii) aware of mosquito bites as the sole cause of malaria (AOR = 7.43; p = 0.008); iii) not sleeping around the kitchen fire (AOR = 24.57; p = 0.001); and iv) having sufficient number of ITNs in the household (AOR = 21.69; p = 0.001).

Conclusion

This study showed how social factors rooted in poverty and swidden agriculture limited the effective use of ITNs, despite high coverage, among ethnic minority populations in Central Vietnam. An in-depth understanding of the local context is essential to develop specific indicators for measuring ITN use.
Tenfold difference in DNA recovery rate: systematic comparison of whole blood vs. dried blood spot sample collection for malaria molecular surveillance
Authors: Holzschuh Aurel , Koepfli Cristian
Published: March 2022

Background

Molecular and genomic surveillance is becoming increasingly used to track malaria control and elimination efforts. Blood samples can be collected as whole blood and stored at − 20 °C until DNA extraction, or as dried blood spots (DBS), circumventing the need for a cold chain. Despite the wide use of either method, systematic comparisons of how the method of blood sample preservation affects the limit of detection (LOD) of molecular diagnosis and the proportion of DNA recovered for downstream applications are lacking.

Methods

Extractions based on spin columns, magnetic beads, Tween-Chelex, and direct PCR without prior extraction were compared for whole blood and dried blood spots (DBS) using dilution series of Plasmodium falciparum culture samples. Extracted DNA was quantified by qPCR and droplet digital PCR (ddPCR).

Results

DNA recovery was 5- to 10-fold higher for whole blood compared to DBS, resulting in a 2- to 3-fold lower LOD for both extraction methods compared to DBS. For whole blood, a magnetic bead-based method resulted in a DNA recovery rate of 88–98% when extracting from whole blood compared to 17–33% for a spin-column based method. For extractions from DBS, the magnetic bead-based method resulted in 8–20% DNA recovery, while the spin-column based method resulted in only 2% DNA recovery. The Tween-Chelex method was superior to other methods with 15–21% DNA recovery, and even more sensitive than extractions from whole blood samples. The direct PCR method was found to have the lowest LOD overall for both, whole blood and DBS.

Conclusions

Pronounced differences in LOD and DNA yield need to be considered when comparing prevalence estimates based on molecular methods and when selecting sampling protocols for other molecular surveillance applications.
Maternal exposure to CeO2NPs derails placental development through trophoblast dysfunction mediated by excessive autophagy activation
Authors: Chen Zhuxiu , Geng Yanqing , Gao Rufei , Zhong Hangtian , Chen Jun , Mu Xinyi , Chen Xuemei , Zhang Yan , Li Fangfang , He Junlin
Published: March 2022

Background

The increasing use of cerium dioxide nanoparticles (CeO2NPs) in biomedical field has attracted substantial attention about their potential risks to human health. Recent studies have shown that nanoparticles can induce placental dysfunction and even fetal abortion, but a more detailed mechanism of nanoparticles affecting placental development remains elusive.

Results

Here, we constructed a mouse exposure model with different doses of CeO2NPs (2.5, 4, 5, 7.5, and 10 mg kg−1 day−1, average particle size 3–5 nm), finding that intravenous exposure to pregnant mice with CeO2NPs could cause abnormal placental development. Deposited nanoparticles were able to be observed in the placental trophoblast at doses of 5 and 7.5 mg kg−1 day−1. Diving into molecular mechanisms indicated that CeO2NPs exposure could lead to autophagy activation in placental trophoblast. At the cellular level, exposure to CeO2NPs inhibited the migration and invasion of HTR-8/SVneo and activated the autophagy through mammalian target of rapamycin complex1 (mTORC1) signaling pathway. Furthermore, inhibition of autophagy initiation by 3-Methyladenine (3-MA) partially restored the function of HTR-8/SVneo, while blocking autophagic flow by Chloroquine (CQ) aggravated the functional damage.

Conclusions

Maternal exposure to CeO2NPs impairs placental development through trophoblast dysfunction mediated by excessive autophagy activation. These results suggested that autophagy dysfunction may be a potential mechanism for the impairment of trophoblast by CeO2NPs exposure. As above, our findings provide insights into the toxicity mechanism to the reproductive system induced by rare-earth nanoparticles exposure.

Graphical Abstract
Metallic phase enabling MoS2 nanosheets as an efficient sonosensitizer for photothermal-enhanced sonodynamic antibacterial therapy
Authors: Chen Huizhi , He Xiaojun , Zhou Zhan , Wu Zhikang , Li Hai , Peng Xinsheng , Zhou Yubin , Tan Chaoliang , Shen Jianliang
Published: March 2022

Two-dimensional (2D) transition metal dichalcogenide (TMD) nanosheets (e.g., MoS2) with metallic phase (1T or 1T´ phase) have been proven to exhibit superior performances in various applications as compared to their semiconducting 2H-phase counterparts. However, it remains unclear how the crystal phase of 2D TMD nanosheets affects their sonodynamic property. In this work, we report the preparation of MoS2 nanosheets with different phases (metallic 1T/1T´ or semiconducting 2H) and exploration of its crystal-phase effect on photothermal-enhanced sonodynamic antibacterial therapy. Interestingly, the defective 2D MoS2 nanosheets with high-percentage metallic 1T/1T´ phase (denoted as M-MoS2) present much higher activity towards the ultrasound-induced generation of reactive oxygen species (ROS) as compared to the semiconducting 2H-phase MoS2 nanosheets. More interestingly, owing to its metallic phase-enabled strong absorption in the near-infrared-II (NIR-II) regime, the ultrasound-induced ROS generation performance of the M-MoS2 nanosheets can be further enhanced by the photothermal effect under a 1064 nm laser irradiation. Thus, after modifying with polyvinylpyrrolidone, the M-MoS2 nanosheets can be used as an efficient sonosensitizer for photothermal-enhanced sonodynamic bacterial elimination under ultrasound treatment combining with NIR-II laser irradiation. This study demonstrates that metallic MoS2 nanosheets can be used as a promising sonosensitizer for antibacterial therapy, which might be also promising for cancer therapies.

Graphical Abstract
Engineering stem cells to produce exosomes with enhanced bone regeneration effects: an alternative strategy for gene therapy
Authors: Li Feiyang , Wu Jun , Li Daiye , Hao Liuzhi , Li Yanqun , Yi Dan , Yeung Kelvin W. K. , Chen Di , Lu William W. , Pan Haobo , Wong Tak Man , Zhao Xiaoli
Published: March 2022

Background

Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as “cell-free” therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency.

Results

In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells.

Conclusions

In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy.

Graphical Abstract
Setting the policy agenda for the treatment of substance use disorders in Iran
Authors: Mirzaei Saeid , Yazdi-Feyzabadi Vahid , Mehrolhassani Mohammad Hossein , Nakhaee Nouzar , Oroomiei Nadia
Published: March 2022

Background

Drug use is one of the most common public health problems globally. This study was done to analyze the agenda-setting of policies related to substance use disorder treatment in Iran since 1979.

Methods

The current qualitative study was done through document review and interviews with policymakers and executives. Purposive sampling with snowball strategy was considered for sampling. Semi-structured interviews were done. A total of 22 documents were examined, and the data were saturated with 32 interviews. Kingdon's Multiple Streams Framework was used to analyze the data.

Results

The results indicated the intersection of problem stream, policy stream, political stream, and opening the opportunity window. In the problem stream, the rapid growth of AIDS among people who inject drugs (PWID), the decrease in the average age of first drug use, the increase in the prevalence of substance use disorder in women, the ineffectiveness of compulsive treatment, and criminological perspectives played key roles. The policy stream included criminological perspective and war on drugs, and harm reduction. The political stream included announcing general anti-narcotics policies by the Supreme Leader of Iran and understanding the need for treatment, rehabilitation, harm reduction, and social support for substance use disorder by officials and policymakers.

Conclusions

For a long time in Iran, policies based on the war on drugs were the dominant approach, and then, policies based on harm reduction and patient-centeredness were considered. The ideology and political parties influenced the executive apparatus's policy stream in this area. In countries with an ideological approach, the political stream plays a critical role in setting issues on the agenda. Therefore, policy entrepreneurs can put the points on the agenda by attracting the attention of political forces to the issue.
Rheumatic fever in a developed country – is it still relevant? A retrospective, 25 years follow-up
Authors: Tal Rotem , Hamad Saied Mohamad , Zidani Razi , Levinsky Yoel , Straussberg Rachel , Amir Jacob , Amarilyo Gil , Harel Liora
Published: March 2022

Background

Our aims were to clinically and epidemiologically characterize rheumatic fever (RF) in the current era in Israel. Although there has been a steady decline in the incidence of RF in the western world, evidence of disease resurgence in developed countries continues to be published. The paucity of recent epidemiological data prompted our study.

Methods

Medical files were retrospectively reviewed for all children with RF in our tertiary pediatric university-affiliated hospital from 1993 to 2017. Main outcome measures were patients and disease related characteristics, incidence trends, risk factors, disease course, relapse rates and secondary prophylaxis.

Results

The cohort included 307 children. Sixty-four percent presented with arthritis, interestingly including hips and small joints of hands and feet at presentation, 52% presented with carditis. Severe carditis developed in 31 patients (19.5%), of whom 21 (13.2% of all carditis patients) acquired heart failure, 5 required intensive care monitoring, with one recent death. The percentage of patients with acute carditis of the overall RF patients remained relatively stable. Thirty-two patients (10% of patients with RF) relapsed, including 11 with a cardiac relapse (3.6% of all cardiac patients). The recurrence rate of RF continued to rise up to 9 years from the initial episode. One of 147 patients (< 0.7%) with a non-cardiac initial presentation had carditis at relapse.

Conclusion

RF and rheumatic heart disease remain an important cause of morbidity and mortality including developed countries, with relapse rate continuing after 9 years of prophylaxis. Presentation of small joints as well as hips, although uncommon, should not exclude the diagnosis.
COVID-19 epidemic in New York City: development of an age group-specific mathematical model to predict the outcome of various vaccination strategies
Authors: Li Miaolei , Zu Jian , Zhang Yue , Ma Le , Shen Mingwang , Li Zongfang , Ji Fanpu
Published: March 2022

Background

Since December 14, 2020, New York City (NYC) has started the first batch of COVID-19 vaccines. However, the shortage of vaccines is currently an inevitable problem. Therefore, optimizing the age-specific COVID-19 vaccination is an important issue that needs to be addressed as a priority.

Objective

Combined with the reported COVID-19 data in NYC, this study aimed to construct a mathematical model with five age groups to estimate the impact of age-specific vaccination on reducing the prevalence of COVID-19.

Methods

We proposed an age-structured mathematical model and estimated the unknown parameters based on the method of Markov Chain Monte Carlo (MCMC). We also calibrated our model by using three different types of reported COVID-19 data in NYC. Moreover, we evaluated the reduced cumulative number of deaths and new infections with different vaccine allocation strategies.

Results

Compared with the current vaccination strategy in NYC, if we gradually increased the vaccination coverage rate for only one age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 75–100 age group would be reduced the most, about 72 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0–17 age group would be reduced the most, about 21,591 fewer new infections per increased 100,000 vaccinated individuals. If we gradually increased the vaccination coverage rate for two age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 65–100 age group would be reduced the most, about 36 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0–44 age group would be reduced the most, about 17,515 fewer new infections per increased 100,000 vaccinated individuals. In addition, if we had an additional 100,000 doses of vaccine for 0–17 and 75–100 age groups as of June 1, 2021, then the allocation of 80% to the 0–17 age group and 20% to the 75–100 age group would reduce the maximum numbers of new infections and deaths simultaneously in NYC.

Conclusions

The COVID-19 burden including deaths and new infections would decrease with increasing vaccination coverage rate. Priority vaccination to the elderly and adolescents would minimize both deaths and new infections.
Innovation of strip fertilization planting for rice straw crushing with back-throwing and interrow-laying
Authors: Shi Yinyan , Jiang Ye , Wang Xiaochan , Yu Haiming , Liu Hui , Chen Jingbo
Published: March 2022

Background

In order to improve the current situations in rice–wheat rotation region in the middle and lower reaches of the Yangtze River, such as large amount of rice straw, complex returning process, short-time stubble connection, high power consumption, poor smoothness and especially unstable performance, and further promote the resource utilization process of full straw returning in Jiangsu province, this study, combined with the agronomic requirements of wheat sowing in rice-stubble land, developed an innovation of strip fertilization planting for straw crushing with back-throwing and interrow-laying in full stubble fields.

Results

Structural design and theoretical analysis were carried out on key components such as straw crushing device, broken-straw control device, soil rotary-tillage device and power transmission device, etc., to determine the corresponding structure and operating performance parameters, and then the field performance and verification tests were completed on the uniformity of inter-row mulching-straw Y1 and the variability of seed-band width Y2. The results showed that the crushing spindle rotation-speed A had an extremely significant impact on Y1, followed by the machine ground speed B. The conveying impeller rotation-speed C had an extremely significant effect on Y2, also secondary to the machine ground speed B. And the superior combination of factor levels as A2B2C2 was adopted through the comprehensive power energy consumption analysis. The verification test results indicated that under the optimized operation parameter combination, namely, when the crushing spindle rotation-speed A was 2100 r/min, the machine ground speed B was 0.8 m/s, and the conveying impeller rotation-speed C was 210 r/min, the mean value of inter-row straw uniformity Y1 and seed-band width variation Y2 were 90.85% and 10.73%, respectively, after machine operation.

Conclusion

It meets the requirements of operation quality and planting agronomy of relevant protective tillage machinery, and provides technical and equipment support for the research and development of similar straw crushing and no-tillage sowing.
Safety and efficacy of minimally invasive McKeown esophagectomy in 1023 consecutive esophageal cancer patients: a single-center experience
Authors: Zheng Xiao-Dong , Li Shi-Cong , Lu Chao , Zhang Wei-Ming , Hou Jian-Bin , Shi Ke-Feng , Zhang Peng
Published: March 2022

Objective

By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center.

Methods

This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan–Meier method.

Results

For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%).

Conclusions

This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications’ morbidity, and acceptable long-term oncologic results.