bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare system resilience in Bangladesh and Haiti in times of global changes (climate-related events, migration and Covid-19): an interdisciplinary mixed method research protocol
Authors: Clech Lucie , Meister Sofia , Belloiseau Maeva , Benmarhnia Tarik , Bonnet Emmanuel , Casseus Alain , Cloos Patrick , Dagenais Christian , De Allegri Manuela , du Loû Annabel Desgrées , Franceschin Lucas , Goudet Jean-Marc , Henrys Daniel , Mathon Dominique , Matin Mowtushi , Queuille Ludovic , Sarker Malabika , Turenne Charlotte Paillard , Ridde Valéry
Published: March 2022

Background

Since climate change, pandemics and population mobility are challenging healthcare systems, an empirical and integrative research to studying and help improving the health systems resilience is needed. We present an interdisciplinary and mixed-methods research protocol, ClimHB, focusing on vulnerable localities in Bangladesh and Haiti, two countries highly sensitive to global changes. We develop a protocol studying the resilience of the healthcare system at multiple levels in the context of climate change and variability, population mobility and the Covid-19 pandemic, both from an institutional and community perspective.

Methods

The conceptual framework designed is based on a combination of Levesque’s Health Access Framework and the Foreign, Commonwealth and Development Office’s Resilience Framework to address both outputs and the processes of resilience of healthcare systems. It uses a mixed-method sequential exploratory research design combining multi-sites and longitudinal approaches. Forty clusters spread over four sites will be studied to understand the importance of context, involving more than 40 healthcare service providers and 2000 households to be surveyed. We will collect primary data through questionnaires, in-depth and semi-structured interviews, focus groups and participatory filming. We will also use secondary data on environmental events sensitive to climate change and potential health risks, healthcare providers’ functioning and organisation. Statistical analyses will include event-history analyses, development of composite indices, multilevel modelling and spatial analyses.

Discussion

This research will generate inter-disciplinary evidence and thus, through knowledge transfer activities, contribute to research on low and middle-income countries (LMIC) health systems and global changes and will better inform decision-makers and populations.
Stroke unit demand in Norway – present and future estimates
Authors: Dahl Fredrik A. , Barra Mathias , Faiz Kashif W. , Ihle-Hansen Hege , Næss Halvor , Rand Kim , Rønning Ole Morten , Simonsen Tone Breines , Thommessen Bente , Labberton Angela S.
Published: March 2022

Background

All stroke patients should receive timely admission to a stroke unit (SU). Consequently, most patients with suspected strokes – including stroke mimics (SM) are admitted. The aim of this study was to estimate the current total demand for SU bed capacity today and give estimates for future (2020–2040) demand.

Methods

Time trend estimates for stroke incidence and time constant estimates for length of stay (LOS) were estimated from the Norwegian Patient Registry (2010–2015). Incidence and LOS models for SMs were based on data from Haukeland University Hospital (2008–2017) and Akershus University Hospital (2020), respectively. The incidence and LOS models were combined with scenarios from Statistic Norway’s population predictions to estimate SU demands for each health region. A telephone survey collected data on the number of currently available SU beds.

Results

In 2020, 361 SU beds are available, while demand was estimated to 302. The models predict a reduction in stroke incidence, which offsets projected demographic shifts. Still, the estimated demand for 2040 rose to 316, due to an increase in SMs. A variation of this reference scenario, where stroke incidence was frozen at the 2020-level, gave a 2040-demand of 480 beds.

Conclusions

While the stroke incidence is likely to continue to fall, this appears to be balanced by an increase in SMs. An important uncertainty is how long the trend of decreasing stroke incidence can be expected to continue. Since the most important uncertainty factors point toward a potential increase, which may be as large as 50%, we would recommend that the health authorities plan for a potential increase in the demand for SU bed capacity.
An innovative case management intervention for people at high risk of permanent work disability to improve rehabilitation coverage and coordination of health services: a randomized controlled trial (AktiFAME, DRKS00024648)
Authors: Remus Lea , Grope Marei , Lemke Stella , Bethge Matthias
Published: March 2022

Background

German social law offers services from various providers and agencies for people with chronic disease or disability. Claiming services requires a high level of information and communication. Dealing with a multitude of actors, such as pension insurance agencies, job centers, employers, physicians, and psychotherapists, and coordinating between and with these actors can delay or prevent the utilization of necessary measures like medical or vocational rehabilitation. We developed a case management intervention for people at high risk of receiving a disability pension to address these challenges.

Methods/design

Our randomized controlled trial tests the effectiveness of the multi-component AktiFAME strategy (Active access, counseling, and case management for people at high risk of permanent work disability). This strategy is comprised of four modules: screening and postal contact, telephone counseling, an initial one-on-one interview, and case management. The randomized controlled trial is complemented by an observational study that exclusively involves the individuals participating in case management and accompanies the implementation of the case management intervention. We enroll 9000 individuals aged 18 to 65 years who were identified as being at increased risk for receiving a disability pension based on administrative data from the German Pension Insurance North but who have not yet applied for rehabilitation. Half of the individuals are randomly assigned to the intervention group and the other half to the control group. The intervention group is contacted and informed about a case management intervention, whereas the control group is not. The primary outcome of the randomized controlled trial is the utilization of rehabilitation services from the German Pension Insurance North (medical or vocational rehabilitation). Data on rehabilitation will be provided by the German Pension Insurance North 1 year after random allocation. Secondary and tertiary outcomes cover additional administrative data (e.g., employment and welfare benefits) and a range of patient-reported outcome measures.

Discussion

This randomized controlled trial is designed to determine the effectiveness of a newly implemented multi-component strategy to promote participation and rehabilitation coverage among individuals at high risk of receiving a disability pension.

Trial registration

German Clinical Trials Register (DRKS00024648, April 27, 2021).
Readmissions performance and penalty experience of safety-net hospitals under Medicare’s Hospital Readmissions Reduction Program
Authors: Banerjee Souvik , Paasche-Orlow Michael K. , McCormick Danny , Lin Meng-Yun , Hanchate Amresh D.
Published: March 2022

Background

The Hospital Readmissions Reduction Program (HRRP), established by the Centers for Medicare and Medicaid Services (CMS) in March 2010, introduced payment-reduction penalties on acute care hospitals with higher-than-expected readmission rates for acute myocardial infarction (AMI), heart failure, and pneumonia. There is concern that hospitals serving large numbers of low-income and uninsured patients (safety-net hospitals) are at greater risk of higher readmissions and penalties, often due to factors that are likely outside the hospital’s control. Using publicly reported data, we compared the readmissions performance and penalty experience among safety-net and non-safety-net hospitals.

Methods

We used nationwide hospital level data for 2009-2016 from the Centers for Medicare and Medicaid Services (CMS) Hospital Compare program, CMS Final Impact Rule, and the American Hospital Association Annual Survey. We identified as safety-net hospitals the top quartile of hospitals in terms of the proportion of patients receiving income-based public benefits. Using a quasi-experimental difference-in-differences approach based on the comparison of pre- vs. post-HRRP changes in (risk-adjusted) 30-day readmission rate in safety-net and non-safety-net hospitals, we estimated the change in readmissions rate associated with HRRP. We also compared the penalty frequency among safety-net and non-safety-net hospitals.

Results

Our study cohort included 1915 hospitals, of which 479 were safety-net hospitals. At baseline (2009), safety-net hospitals had a slightly higher readmission rate compared to non-safety net hospitals for all three conditions: AMI, 20.3% vs. 19.8% (p value< 0.001); heart failure, 25.2% vs. 24.2% (p-value< 0.001); pneumonia, 18.7% vs. 18.1% (p-value< 0.001). Beginning in 2012, readmission rates declined similarly in both hospital groups for all three cohorts. Based on difference-in-differences analysis, HRRP was associated with similar change in the readmissions rate in safety-net and non-safety-net hospitals for AMI and heart failure. For the pneumonia cohort, we found a larger reduction (0.23%; p < 0.001) in safety-net hospitals. The frequency of readmissions penalty was higher among safety-net hospitals. The proportion of hospitals penalized during all four post-HRRP years was 72% among safety-net and 59% among non-safety-net hospitals.

Conclusions

Our results lend support to the concerns of disproportionately higher risk of performance-based penalty on safety-net hospitals.
Identification and pathogenicity of hepatitis E Virus from laboratory Bama miniature pigs
Authors: Liu Baoyuan , Chen Yiyang , Zhang Meimei , Chen Tianxiang , Zhang Yuan , DanBaZhaXi  , Xu Shixuan , Zhao Qin , Zhou En-Min
Published: March 2022

Background

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic. In this study, HEV infection in laboratory Bama miniature pigs in Sichuan Province of China was investigated. Firstly, one hundred rectal swabs were collected for HEV RNA testing, and chose positive samples for sequence analysis. Concurrently, for pathogenicity study, six healthy Bama miniature pigs were randomly divided into two groups of 3 pigs each. A total of 500 μL of HEV stock (positive fecal samples identified in this study) was inoculated intravenously into each pig in the experimental group, and the three pigs in the other group served as negative controls. Serum and fecal samples were collected at 1 to 10 weeks post-inoculation (wpi) for alanine aminotransferase (ALT) levels, anti-HEV antibodies and HEV RNA detection, respectively. During necropsies, liver lesions and HEV antigen in liver were observed at 10 wpi.

Results

The rate of fecal sample HEV RNA-positivity was 12% (12/100). Sequence comparisons indicated that partial ORF1 and ORF2 gene sequences of this isolate shared highest identities with corresponding sequences of genotype 4a HEV isolates (81.4%-96.1% and 89.9%-97.1%, respectively). Phylogenetic tree analysis further demonstrated that sequences of this isolate clustered together with sub-genotype 4a HEV isolate sequences. Experimentally, the pathogenicity of Bama miniature pigs infected with this isolate exhibited viremia, fecal virus shedding, seroconversion, ALT level increasing, liver lesions and HEV antigen in liver.

Conclusions

This is the first study to confirm that HEV is currently circulating in laboratory Bama miniature pigs in China and this isolate can successfully infect Bama miniature pigs experimentally. More importantly, this study suggested HEV screening of laboratory pigs should be conducted to prevent research personnel from acquiring zoonotic HEV infections.
Sex-specific associations of fat mass and muscle mass with cardiovascular disease risk factors in adults with type 2 diabetes living with overweight and obesity: secondary analysis of the Look AHEAD trial
Authors: Terada Tasuku , Reed Jennifer L. , Vidal-Almela Sol , Mistura Matheus , Kamiya Kentaro , Way Kimberley L.
Published: March 2022

Background

Distinguishable sex differences exist in fat mass and muscle mass. High fat mass and low muscle mass are independently associated with cardiovascular disease (CVD) risk factors in people living with type 2 diabetes; however, it is unknown if the association between fat mass and CVD risk is modified by muscle mass, or vice versa. This study examined the sex-specific interplay between fat mass and muscle mass on CVD risk factors in adults with type 2 diabetes living with overweight and obesity.

Methods

Dual-energy X-ray absorptiometry (DXA) measures were used to compute fat mass index (FMI) and appendicular muscle mass index (ASMI), and participants were separated into high-fat mass vs. low-fat mass and high-muscle mass vs. low-muscle mass. A two-way analysis of covariance (ANCOVA: high-FMI vs. low-FMI by high-ASMI vs. low-ASMI) was performed on CVD risk factors (i.e., hemoglobin A1C [A1C]; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; triglycerides; systolic and diastolic blood pressure; cardiorespiratory fitness, depression and health related-quality of life [HR-QoL]) at baseline and following a 1-year intensive lifestyle intervention (ILI) for females and males separately, with a primary focus on the fat mass by muscle mass interaction effects.

Results

Data from 1,369 participants (62.7% females) who completed baseline DXA were analyzed. In females, there was a fat mass by muscle mass interaction effect on A1C (p = 0.016) at baseline. Post-hoc analysis showed that, in the low-FMI group, A1C was significantly higher in low-ASMI when compared to high-ASMI (60.3 ± 14.1 vs. 55.5 ± 13.5 mmol/mol, p = 0.023). In the high-FMI group, there was no difference between high-ASMI and low-ASMI (56.4 ± 12.5 vs. 56.5 ± 12.8 mmol/mol, p = 0.610). In males, only high-FMI was associated with higher A1C when compared to low-FMI (57.1 ± 14.4 vs. 54.2 ± 12.0 mmol/mol, p = 0.008) at baseline. Following ILI, there were significant fat mass by muscle mass interaction effects on changes in the mental component of HR-QoL in males.

Conclusion

Considering that A1C predicts future CVD, strategies to lower A1C may be especially important in females with low fat and low muscle mass living with type 2 diabetes. Our results highlight the complicated and sex-specific contribution of fat mass and muscle mass to CVD risk factors.
Identification of proteomic markers for prediction of the response to 5-Fluorouracil based neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients
Authors: Wang Jianan , Liu Jiayu , Wang Jinyang , Wang Shijian , Li Feifei , Li Ruibing , Liu Peng , Li Mianyang , Wang Chengbin
Published: March 2022

Background

Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is the standard treatment for patients with locally advanced rectal cancer (LARC), while parts of them show poor therapeutic response accompanied by therapy adverse effects. Predictive biomarkers for nCRT response could facilitate the guidance on treatment decisions but are still insufficient until now, which limits the clinical applications of nCRT in LARC patients.

Methods

In our study, 37 formalin-fixed paraffin-embedded tumor biopsies were obtained from patients with LARC before receiving 5-fluorouracil based nCRT. Proteomics analyses were conducted to identify the differentially expressed proteins (DEPs) between total responders (TR) and poor responders (PR). The DEPs were validated via ROC plotter web tool and their predictive performance was evaluated by receiver operating characteristic analysis. Functional enrichment analyses were performed to further explore the potential mechanisms underlying nCRT response.

Results

Among 3,998 total proteins, 91 DEPs between TR and PR were screened out. HSPA4, NIPSNAP1, and SPTB all with areas under the curve (AUC) ~ 0.8 in the internal discovery cohort were independently validated by the external mRNA datasets (AUC ~ 0.7), and their protein levels were linearly correlated with the graded responses to nCRT in the internal cohort. The combination of HSPA4 and SPTB could distinctly discriminate the TR and PR groups (AUC = 0.980, p < 0.0001). Moreover, multiple combinations of the three proteins realized increased specificity and/or sensitivity, while achieving favorable predictive value when moderate responders were introduced into the ROC analysis. Pathways including DNA damage repair, cell cycle, and epithelial mesenchymal transition were involved in nCRT response according to the enrichment analysis results.

Conclusions

HSPA4, SPTB and NIPSNAP1 in tumor biopsies and/or their optional combinations might be potential predictive markers for nCRT response in patients with LARC. The DEPs and their related functions have implications for the potential mechanisms of treatment response to nCRT in patients with LARC.
Key factors associated with malaria infection among patients seeking care through the public sector in endemic townships of Ayeyarwady Region, Myanmar
Authors: Dunning Jillian , Aung Nang Khaing Zar , Ward Abigail , Aye Moe Moe , Lourenço Christopher , Gallalee Sarah , Lavenberg Stephen , Le Menach Arnaud , Tun Myat Min , Thi Aung
Published: March 2022

Background

Ayeyarwady Region in Myanmar has made significant progress towards malaria elimination, with cases decreasing from 12,312 in 2015 to 122 in 2019. As transmission declines, malaria becomes increasingly focalized both in geographic hotspots and among population groups sharing certain risk factors. Developing a thorough profile of high-risk activities associated with malaria infections is critical to ensure intervention approaches are evidence-based.

Methods

A test-negative study was conducted from September 2017 to May 2018 in Ngaputaw, Pathein and Thabaung townships in Ayeyarwady Region. Patients that presented to selected public facilities or community health volunteers with fever answered survey questions on demographic and behavioural risk factors, including exposure to malaria interventions, and were assigned to case and control groups based on the result of a malaria rapid diagnostic test. A random-effects logistic regression model adjusted for clustering at the facility level, as well as any variables along the causal pathway described by a directed acyclic graph, was used to determine odds ratios and association with malaria infections.

Results

A total of 119 cases and 1744 controls were recruited from 41 public facilities, with a mean age of 31.3 and 63.7% male. Higher risk groups were identified as males (aOR 1.8, 95% CI 1.2–2.9) and those with a worksite located within the forest (aOR 2.8, 95% CI 1.4–5.3), specifically working in the logging (aOR 2.7, 95% CI 1.5–4.6) and rubber plantation (aOR 3.0, 95% CI 1.4–6.8) industries. Additionally, links between forest travel and malaria were observed, with risk factors identified to be sleeping in the forest within the past month (aOR 2.6, 95% CI 1.1–6.3), and extended forest travel with durations from 3 to 14 days (aOR 8.6, 95% CI 3.5–21.4) or longer periods (aOR 8.4, 95% CI 3.2–21.6).

Conclusion

Malaria transmission is highly focalized in Ayeyarwady, and results illustrate the need to target interventions to the most at-risk populations of working males and forest goers. It will become increasingly necessary to ensure full intervention coverage of at-risk populations active in forested areas as Myanmar moves closer to malaria elimination goals.
Developing a tool for the measurement of social exclusion in healthcare settings
Authors: O’Donnell Patrick , Hannigan Ailish , Ibrahim Nuha , O’Donovan Diarmuid , Elmusharaf Khalifa
Published: March 2022

Background

Social exclusion is a complex concept that is recognised as a key determinant of health. Many measurement tools developed looked at people from single excluded groups in isolation. We know from experience and literature that exclusion is often intersectional and multi-layered. Therefore, the aim of this research was to develop a social exclusion measurement tool for use in healthcare settings with individuals from any excluded group that would include questions to investigate socioeconomic elements and subjective experiences in their lives.

Methods

Inductive and deductive methods were used to develop the tool. Early drafts were tested with experts (both academic and experts by experience) and modified in line with feedback received. The tool was then piloted with people in the community, and this allowed us to assess the internal consistency and validity of the tool. Exploratory factor analysis was carried out as part of this evaluation.

Results

The measurement tool was initially evaluated by 17 academic and ‘real world’ experts. It was then piloted with seven experts by experience, two gatekeepers and two participants who were presumed not to be excluded, resulting in the development of the final tool. This was then tested with 276 participants (127 presumed excluded, 149 presumed not excluded). The socioeconomic characteristics of these participants were documented, and exploratory factor analysis was carried out on data relating to subjective items. A four-factor structure emerged comprising 22 items. Internal consistency of the factors was high, and their ability to discriminate between the two groups was notable.

Conclusions

A tool for measuring the social exclusion of individuals has been developed by engaging with people from a variety of excluded groups. Socioeconomic indicators were combined with subjective items. The input of experts by experience, academics and others was sought to enhance the tool. The tool was applied to two distinct samples, showing obvious differences both in the socioeconomic items, and the items included in the factor analysis. The potential use of this tool could have positive implications for people who are excluded.
Early diagnosis of breast cancer lung metastasis by nanoprobe-based luminescence imaging of the pre-metastatic niche
Authors: Zheng Hanwen , Yuan Chunsen , Cai Jiajun , Pu Wendan , Wu Peng , Li Chenwen , Li Gang , Zhang Yang , Zhang Jianxiang , Guo Jiawei , Huang Dingde
Published: March 2022

Background

Early detection of breast cancer lung metastasis remains highly challenging, due to few metastatic cancer cells at an early stage. Herein we propose a new strategy for early diagnosis of lung metastasis of breast cancer by luminescence imaging of pulmonary neutrophil infiltration via self-illuminating nanoprobes.

Methods

Luminescent nanoparticles (LAD NPs) were engineered using a biocompatible, neutrophil-responsive self-illuminating cyclodextrin material and an aggregation-induced emission agent. The chemiluminescence resonance energy transfer (CRET) effect and luminescence properties of LAD NPs were fully characterized. Using mouse peritoneal neutrophils, in vitro luminescence properties of LAD NPs were thoroughly examined. In vivo luminescence imaging and correlation analyses were performed in mice inoculated with 4T1 cancer cells. Moreover, an active targeting nanoprobe was developed by surface decoration of LAD NPs with a neutrophil-targeting peptide, which was also systemically evaluated by in vitro and in vivo studies.

Results

LAD NPs can generate long-wavelength and persistent luminescence due to the CRET effect. In a mouse model of 4T1 breast cancer lung metastasis, we found desirable correlation between neutrophils and tumor cells in the lungs, demonstrating the effectiveness of early imaging of the pre-metastatic niche by the newly developed LAD NPs. The active targeting nanoprobe showed further enhanced luminescence imaging capability for early detection of pulmonary metastasis. Notably, the targeting nanoprobe-based luminescence imaging strategy remarkably outperformed PET/CT imaging modalities in the examined mouse model. Also, preliminary tests demonstrated good safety of LAD NPs.

Conclusions

The neutrophil-targeting imaging strategy based on newly developed luminescence nanoparticles can serve as a promising modality for early diagnosis of lung metastasis of breast cancers.

Graphical Abstract
Enhanced tumor accumulation and therapeutic efficacy of liposomal drugs through over-threshold dosing
Authors: Ao Hui , Wang Zhuo , Lu Likang , Ma Hongwei , Li Haowen , Fu Jingxin , Li Manzhen , Han Meihua , Guo Yifei , Wang Xiangtao
Published: March 2022

Background

Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible.

Methods

Referring to Ouyang’s work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent probe, to trace their in vivo biodistribution. Two mouse models, 4T1-bearing and U87-bearing, were employed for in vivo examination.

Results

PEG-Lipo and PEG-ACGs-Lipo had similar diameters. At a low-threshold dose (12 mg/kg equivalent phospholipids), PEG-Lipo was mainly distributed in the liver rather than in the tumor, with the relative tumor targeting index (RTTI) being ~ 0.38 at 72 h after administration. When over-threshold was administered (50 mg/kg or 80 mg/kg of equivalent phospholipids), a much higher and quicker drug accumulation in tumors and a much lower drug accumulation in the liver were observed, with the RTTI increasing to ~ 0.9. The in vivo antitumor study in 4T1 tumor-bearing mice showed that, compared to PEG-ACGs-Lipo alone (2.25 mg/kg phospholipids), the co-injection of a large dose of blank PEG-Lipo (50 mg/kg of phospholipids) significantly reduced the tumor volume of the mice by 22.6% (P < 0.05) and enhanced the RTTI from 0.41 to 1.34. The intravenous injection of a low drug loading content (LDLC) of liposomal ACGs (the same dose of ACGs at 50 mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P < 0.05) and survival time of PEG-ACGs-Lipo.

Conclusion

An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs.

Graphical Abstract
Changes in cannabis use and associated correlates during France’s first COVID-19 lockdown in daily cannabis users: results from a large community-based online survey
Authors: Mezaache Salim , Donadille Cécile , Martin Victor , Le Brun Gadelius Maëla , Appel Laurent , Spire Bruno , Briand Madrid Laelia , Bastien Martin , Roux Perrine
Published: March 2022

Background

Lockdown measures during the first wave of the COVID-19 pandemic in France led to serious public health concerns over people who use illicit drugs, especially in terms of mental health. We assessed changes in cannabis use during the first lockdown in France among daily cannabis users and associated correlates.

Methods

CANNAVID is a French, national, cross-sectional web-based survey, conducted from 17 April to 11 May 2020. Daily cannabis users aged ≥ 18 years and living in France were invited to participate through advertisements. Respondents completed an ad hoc questionnaire on a dedicated online platform. We analyzed changes in cannabis use during the first lockdown (i.e.,stopped, decreased, unchanged, or increased) and performed a multinomial logistic regression analysis to evaluate correlates of these changes.

Results

Of the 4019 participants, 74.0% were men. Median age was 27 years (interquartile range: 22–37). With regard to cannabis use, 293 (7.3%) persons stopped, 1153 (28.7%) decreased, 1146 (28.5%) did not change, and 1427 (35.5%) increased their use during the lockdown. A multinomial logistic regression model revealed several sociodemographic, behavioral and health-related factors associated with changes in cannabis use. Compared with participants with an unchanged level of cannabis use during the lockdown, those who increased and those who stopped cannabis use were more likely to have increased tobacco and alcohol use and to have experienced depression and sleep disorders intensification. Those who stopped cannabis use were also more likely to have increased benzodiazepine use and to have experienced pain increase during lockdown.

Conclusions

France’s first COVID-19-related lockdown had a differential impact on daily cannabis users’ consumption patterns. Most study respondents reported changes to their cannabis consumption pattern. Those who reported a stable cannabis use were more likely to report fewer negative changes. Specific interventions are needed for this population, as well as research to assess the long-term impacts of these changes.
Laparoscopic segmental colectomy with extensive D3 lymph node dissection: a good choice for right transverse colon cancer
Authors: Huang Xing
Published: March 2022

Background

Previous research was yet to establish a definite operation for transverse colon cancer (TCC); surgical procedure was often dictated by the surgeon’s preference in clinical practice. The main surgical methods could be summarized in two main points: segmental colectomy (transverse colectomy) and right hemicolectomy.

Method

The first patient was a 78-year-old woman, who was diagnosed with right TCC. Computed tomography revealed a right TCC and a very long transverse colon; laparoscopic exploration revealed an enlarged apical lymph node surrounding the ileocolic vessels. We performed a segmental colectomy with extensive apical lymph node dissection along the superior mesenteric vessels and its main branches for her. To distinguish it from the previous radical operations for TCC, we called this operation a segmental colectomy with extensive D3 lymph node dissection. Then, this surgical intervention was performed on 8 other TCC patients.

Results

The total operating time was 158 min. Pathological examination confirmed 2 apical lymph node metastases; among them, one apical lymph node metastasis was in group No.203. For all 9 patients, the median operative time was 160 min (range, 140–185 min), the average number of lymph node retrieval was 30 (range, 25–39), and the average number of apical lymph node (No.203, No.213, and No.223) retrieval was 5.9 (range, 0–11). Because of the preservation of the ileocecal junction and part of the ascending colon, all patients recovered uneventfully after surgery, and long-term diarrhea, water-electrolyte imbalance, and other Clavien–Dindo grade III or greater postoperative complications did not occur.

Conclusions

Our procedure combined the advantages of segmental colectomy and right hemicolectomy and gave consideration to oncological and functional outcomes. It may be an optimal choice for TCC patients with a very long transverse colon and preoperative diagnosis of lymph node metastasis.
Glycogen synthase kinase GSK3α promotes tumorigenesis by activating HIF1/VEGFA signaling pathway in NSCLC tumor
Authors: Cao Xiaonian , Wu Wei , Wang Dao , Sun Wei , Lai Senyan
Published: March 2022

Background

Lung cancer is one of the most common cancers and the leading cause of cancer-related death. Glycogen synthase kinase-3 (GSK-3) α, a member of the glycogen synthase kinase-3 family, reportedly plays a role in tumorigenesis. However, its biological function in tumorigenesis requires deeper exploration. Hypoxia is a major feature of solid tumor, along with decreasing availability of oxygen, inducing treatment resistance, and tumor progress.

Methods

Levels of GSK3α expression in clinical samples were detected using western blot and IHC assays, while its biological function and underlying mechanism of action in tumor progression were investigated using western blot, CCK8, cell cycle, colony formation, Transwell, ELISA and tube formation assays. Furthermore, we investigated the relationship between GSK3α expression and the HIF1α/VEGFA signaling pathway in vivo using a mouse xenograft model.

Results

GSK3α was significantly upregulated in NSCLC patients with cases that exhibited high GSK3α levels recording shorter survival times. Moreover, GSK3α overexpression promoted proliferation, migration, invasion and clone formation ability of NSCLC cells, while its silencing resulted in an opposite phenomenon. Moreover, GSK3α not only activated the HIF1α/VEGFA signaling pathway, but also regulated HIF1α stabilization independently via the PHDs-pVHL signaling pathway. Moreover, GSK3α-mediated tumor angiogenesis depended on HIF1α expression both in vitro and in vivo.

Conclusion

GSK3α functioned as an oncogene in NSCLC tumorigenesis by regulating the HIF1/VEGFA signaling pathway in an independent manner through the PHDs-pVHL signaling pathway. These findings were expected to provide novel sights to guide future development of therapies for effective treatment of NSCLC.
Traditional uses of wild and tended plants in maintaining ecosystem services in agricultural landscapes of the Eastern Cape Province in South Africa
Authors: Maroyi Alfred
Published: March 2022

Background

Many communities in developing countries rely on ecosystem services (ESs) associated with wild and cultivated plant species. Plant resources provide numerous ESs and goods that support human well-being and survival. The aim of this study was to identify and characterize wild and tended plant species, and also investigate how local communities in the Eastern Cape Province in South Africa perceive ESs associated with plant resources.

Methods

The study was conducted in six local municipalities in the Eastern Cape Province, between March 2016 and September 2021. Data on socio-economic characteristics of the participants, useful plants harvested from the wild and managed in home gardens were documented by means of questionnaires, observation and guided field walks with 196 participants. The ESs were identified using a free listing technique.

Results

A total of 163 plant species were recorded which provided 26 cultural, regulating and provisioning ESs. Provisioning ESs were the most cited with at least 25 plant species contributing towards generation of cash income, food, traditional and ethnoveterinary medicines. Important species recorded in this study with relative frequency of citation (RFC) values > 0.3 included Alepidea amatymbica, Allium cepa, Aloe ferox, Artemisia afra, Brassica oleracea, Capsicum annuum, Cucurbita moschata, Hypoxis hemerocallidea, Opuntia ficus-indica, Spinacia oleracea, Vachellia karroo and Zea mays.

Conclusion

Results of this study highlight the importance of plant resources to the well-being of local communities in the Eastern Cape within the context of provision of essential direct and indirect ESs such as food, medicinal products, construction materials, fodder, regulating, supporting and cultural services. The ESs are the basis for subsistence livelihoods in rural areas, particularly in developing countries such as South Africa. Therefore, such body of knowledge can be used as baseline data for provision of local support for natural resource management initiatives in the province and other areas of the country.
Utility of a novel integrated deep convolutional neural network for the segmentation of hip joint from computed tomography images in the preoperative planning of total hip arthroplasty
Authors: Wu Dong , Zhi Xin , Liu Xingyu , Zhang Yiling , Chai Wei
Published: March 2022

Purpose

Preoperative three-dimensional planning is important for total hip arthroplasty. To simulate the placement of joint implants on computed tomography (CT), pelvis and femur must be segmented. Accurate and rapid segmentation of the hip joint is challenging. This study aimed to develop a novel deep learning network, named Changmugu Net (CMG Net), which could achieve accurate segmentation of the femur and pelvis.

Methods

The overall deep neural network architecture of CMG Net employed three interrelated modules. CMG Net included the 2D U-net to separate the bony and soft tissues. The modular hierarchy method was used for the main femur segmentation to achieve better performance. A layer classifier was adopted to localise femur layers among a series of CT scan images. The first module was a modified 2D U-net, which separated bony and soft tissues; it provided intermediate supervision for the main femur segmentation. The second module was the main femur segmentation, which was used to distinguish the femur from the acetabulum. The third module was the layer classifier, which served as a post-processor for the second module.

Results

There was a much greater overlap in accuracy results with the “gold standard” segmentation than with competing networks. The dice overlap coefficient was 93.55% ± 5.57%; the mean surface distance was 1.34 ± 0.24 mm, and the Hausdorff distance was 4.19 ± 1.04 mm in the normal and diseased hips, which indicated greater accuracy than the other four competing networks. Moreover, the mean segmentation time of CMG Net was 25.87 ± 2.73 s, which was shorter than the times of the other four networks.

Conclusions

The prominent segmentation accuracy and run-time of CMG Net suggest that it is a reliable method for clinicians to observe anatomical structures of the hip joints, even in severely diseased cases.
Influence of intervention treatment by “heat-clearing and diuresis-promoting” prescription on NALP3, an inflammatory factor in acute gouty arthritis
Authors: Yu Jun , Li Lianrui , Liu Jie , Chen Zhiyong
Published: March 2022

Background

To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients.

Methods

A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given “heat-clearing and diuresis-promoting” prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment.

Results

After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P < 0.05); the clinical effective rate in the observation group (94.87%) was higher than that in the control group (76.92%). The serum uric acid (UA), erythrocyte sedimentation rate (ESR), interleukin-1β (IL-1β) and NALP3 showed a decreasing trend, and the decrease degree of each index in observation group was higher than that in control group (P < 0.05).

Conclusion

The “heat-clearing and diuresis-promoting” prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect.
Biomechanical analysis of the correlation between mid-shaft atypical femoral fracture (AFF) and axial varus deformation
Authors: Severyns Mathieu , Belaid Dalila , Aubert Kevin , Bouchoucha Ali , Germaneau Arnaud , Vendeuvre Tanguy
Published: March 2022

Background

Atypical femoral fractures (AFF) are diaphyseal fractures of the elderly that occur at the end of a minor trauma. The objective of this biomechanical study, using finite element modelling, was to evaluate the variations of the femoral diaphysis fracture indicator according to the variations of the mechanical axis of the lower limb, which can explain all the different atypical fracture types identified in the literature.

Methods

In order to measure variations in stress and risk factors for fracture of the femoral diaphysis, the distal end of the femur was constrained in all degrees of freedom. An axial compression load was applied to the femoral head to digitally simulate the bipodal support configuration in neutral position as well as in different axial positions in varus/valgus (− 10°/10°).

Results

The maximum stress value of Von Mises was twice as high (17.96 ± 4.87 MPa) at a varus angle of − 10° as in the neutral position. The fracture risk indicator of the femoral diaphysis varies proportionally with the absolute value of the steering angle. However, the largest simulated varus deformation (− 10°) found a higher risk of diaphysis fracture indicator than in valgus (10°).

Conclusions

Variations in the mechanical axis of the lower limb influence the stress distribution at the femur diaphysis and consequently increase the risk of AFF. The axial deformation in varus is particularly at risk of AFF. The combination of axial deformation stresses and bone fragility consequently contribute to the creation of an environment favorable to the development of AFF.

Trial registration: ‘retrospectively registered’.
Comparison of latissimus dorsi tendon transfer with subscapularis release versus sliding of internal rotation contracture in obstetrical brachial plexus paralysis sequela
Authors: Abdelaziz Ashraf M. , AbdAlfattah Mohammed A. , El-sherief Faisal Ahmed Hashem , Wahd Yaser El Sayed Hassan , Soliman Hany Abdel Gawwad , El Behairy Hassan Fathy , Ismail Mahmoud Ali
Published: March 2022

Background

The purpose of this study was to compare the functional results of latissimus dorsi (LD) tendon transfer with those of subscapularis (SS) muscle release versus sliding.

Methods

Fifty-six patients with internal rotation contracture and external rotation (ER) weakness as sequelae of Erb’s palsy were included in the study. Of the patients, 24 were included in group 1 (11 boys and 13 girls), with a mean age of 2 years 8 months (range 1.5–5 years) and a follow-up period of 62 months (range 38–68 months). The patients in group 1 underwent LD tendon transfer, with internal rotation contracture and SS release procedures. Thirty-two patients were included in group 2 (18 boys and 14 girls), with a mean age of 2 years 6 months (range 1.5–4.8 years) and a follow-up period of 58 months (range 38–68 months). The patients in group 2 underwent LD tendon transfer with SS sliding.

Results

A significant improvement in preoperative passive ER from − 3.6° to 67.3° after operation was observed in group 1. In group 2, preoperative passive ER in adduction improved from 0° to 72.3°. We found no significant difference (P = 0.1) in postoperative improvement in active ER in both groups (group 1 vs. group 2: 75° vs. 77.3°). Similarly, no significant difference (P = 0.7) in postoperative improvement in passive ER was found between the groups (group 1 vs. group 2: 71° vs. 72.3°).

Conclusions

LD tendon transfer with SS release or sliding is an effective procedure to improve shoulder ER in patients with OBPP, with no inferiority of SS muscle release or sliding for internal rotation contractures and increased passive range of shoulder motion.

Level of evidence

Level III; Retrospective Cohort Comparison; Treatment Study.
PPP1R26 drives hepatocellular carcinoma progression by controlling glycolysis and epithelial-mesenchymal transition
Authors: Yang Yang , Ren Pengwei , Liu Xiaofeng , Sun Xiaoyan , Zhang Chunfeng , Du Xiaojuan , Xing Baocai
Published: March 2022

Background

Hepatocellular carcinoma (HCC) is usually diagnosed at an advanced stage due to rapid progression. Glycolysis supports anabolic growth and metastasis to promote HCC progression. However, the molecular mechanisms linking glycolysis and metastasis in HCC are not completely defined.

Methods

The expression of PPP1R26 in human HCC tissues was evaluated by immunohistochemistry, and the clinical significance of PPP1R26 in the progression and prognosis of the HCC patients were analyzed. The PPP1R26-binding proteins were determined by mass spectrometry analysis. The function of PPP1R26 in glycolysis, EMT and tumorigenesis were evaluated in HCC cells. Glucose uptake and tumor growth were evaluated using PET imaging in mouse xenografts in vivo. Protein binding was confirmed by co-immunoprecipitation and immunofluorescence co-localization. Protein-RNA binding was determined by RNA-immunoprecipitation (RIP) experiment. The binding of protein on the promoter was evaluated by chromatin immunoprecipitation assay (ChIP).

Results

PPP1R26 is upregulated in human HCC tissues and its upregulation is significantly associated with metastasis and the poor survival of the patients. PPP1R26 activates glycolysis in HCC cells and in mouse xenografts in vivo. PPP1R26 drives glycolysis by binding to PTBP1 to facilitate the mRNA splicing of PKM2. Simultaneously, overexpressed PPP1R26 induces the nuclear accumulation of PKM2 to inhibit the expression of E-cadherin further to drive EMT. Mechanistically, PPP1R26 binds with Ser37-phosphorylated PKM2 and TGIF2 in the nucleus and blocks the binding of TGIF2 with CDH1 promoter to inhibit the transcription of CDH1.

Conclusion

PPP1R26 promotes glycolysis by enhancing PKM2 splicing and simultaneously activates EMT by forming a PPP1R26-PKM2-TGIF2 complex to drive HCC progression. Therefore, targeting PPP1R26 attenuates HCC progression and provides a potential therapeutic strategy for the HCC patients with upregulation of PPP1R26.
Incidental occurrence of neutropenia in children hospitalised for COVID-19
Authors: Folino Francesco , Menis Camilla , Di Pietro Giada Maria , Pinzani Raffaella , Marchisio Paola , Bosis Samantha
Published: March 2022

Background

Investigations on haematological alterations in paediatric COVID-19 have been focused mostly on lymphocytes and clotting profiles. Neutropenia has been occasionally reported and its course and impact on the disease have not been elucidated. The aim of this study was to describe the epidemiology, course, and impact of neutropenia in children with COVID-19 hospitalised in a tertiary care referral paediatric ward.

Methods

A single-centre retrospective study was conducted. Hospitalised children between 1 month and 18 years with confirmed COVID-19 and neutropenia were included and compared to non neutropenic patients. Complete blood picture with differential blood count, serum biochemistry, clotting profiles were performed; clinical data, length of hospitalisation, and prescription of drugs were collected.

Results

Twelve out of 95 patients (12.63%) with documented SARS-CoV-2 infection were neutropenic and met the inclusion criteria. The mean age was 161 days (range 38—490 days). The mean duration of symptoms in neutropenic children was 3.82 days, while the mean length of hospitalisation was 7.67 days. These findings were not significantly different in the two study groups. All patients had mild clinical manifestations and were discharged without sequelae.

Conclusions

We provided the first comprehensive study on neutropenia in mild paediatric COVID-19 infection. Our findings show that the main features of this haematological disorder in COVID-19 are analogous to the well-known transient benign neutropenia associated with other common viral infections. In our setting, neutropenia does not emerge as a potential negative prognostic factor in paediatric COVID-19.