bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of alcohol consumption with the incidence of proteinuria and chronic kidney disease: a retrospective cohort study in Japan
Authors: Tanaka Akio , Yamaguchi Makoto , Ishimoto Takuji , Katsuno Takayuki , Nobata Hironobu , Iwagaitsu Shiho , Sugiyama Hirokazu , Kinashi Hiroshi , Banno Shogo , Imaizumi Takahiro , Ando Masahiko , Kubo Yoko , Ito Yasuhiko
Published: May 2022

Background

The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex.

Methods

This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%).

Results

During a median observational period of 4 years (interquartile range: 2–6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10–2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04–2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men.

Conclusions

In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction.
Highly potent multivalent VHH antibodies against Chikungunya isolated from an alpaca naïve phage display library
Authors: Li Qianlin , Zhang Fuqiang , Lu Yi , Hu Huan , Wang Jin , Guo Cheng , Deng Qiang , Liao Conghui , Wu Qin , Hu Tingsong , Chen Zeliang , Lu Jiahai
Published: May 2022

Background

Chikungunya virus (CHIKV) is a re-emerged mosquito-borne alphavirus that can cause musculoskeletal diseases, imposing a substantial threat to public health globally. High-affinity antibodies are need for diagnosis and treatment of CHIKV infections. As a potential diagnostic and therapeutic agent, the multivalent VHH antibodies is a promising tookit in nanomedicine. Here, we developed potent multivalent VHH antibodies from an alpaca naïve phage display library targeting the E2 glycoprotein of the CHIKV virus.

Results

In the present study, we generated 20 VHH antibodies using a naïve phage display library for binders to the CHIKV E2 glycoprotein. Of these, multivalent VHH antibodies Nb-2E8 and Nb-3C5 had specific high-affinity binding to E2 protein within the nanomolar range. The equilibrium dissociation constant (KD) was between 2.59–20.7 nM, which was 100-fold stronger than the monovalent antibodies’ affinity. Moreover, epitope mapping showed that Nb-2E8 and Nb-3C5 recognized different linear epitopes located on the E2 glycoprotein domain C and A, respectively. A facile protocol of sandwich ELISA was established using BiNb-2E8 as a capture antibody and HRP-conjugated BiNb-3C5 as a detection antibody. A good linear correlation was achieved between the OD450 value and the E2 protein concentration in the 5–1000 ng/mL range (r = 0.9864, P < 0.0001), indicating its potential for quantitative detection of the E2 protein.

Conclusions

Compared to monovalent antibodies, multivalent VHH antibodies Nb-2E8 and Nb-3C5 showed high affinity and are potential candidates for diagnostic applications to better detect CHIKV virions in sera.

Graphical Abstract
Enhancement of antitumor immunotherapy using mitochondria-targeted cancer cell membrane-biomimetic MOF-mediated sonodynamic therapy and checkpoint blockade immunotherapy
Authors: Luo Jiali , Wang Xue , Shi Zhan , Zeng Yiqing , He Liangcan , Cao Jing , Sun Yu , Zhang Tao , Huang Pintong
Published: May 2022

Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal–organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.
A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin
Authors: Yang Xiao-Xin , Xu Xiang , Wang Mei-Fang , Xu Hua-Zhen , Peng Xing-Chun , Han Ning , Yu Ting-Ting , Li Liu-Gen , Li Qi-Rui , Chen Xiao , Wen Yu , Li Tong-Fei
Published: May 2022

Background

Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy.

Results

The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity.

Conclusion

In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.

Graphical Abstract
Association between early ondansetron administration and in-hospital mortality in critically ill patients: analysis of the MIMIC-IV database
Authors: Fang Yingying , Xiong Chao , Wang Xinghe
Published: May 2022

Background

While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose.

Methods

The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings.

Results

In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63–0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34–0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42–0.76; P < 0.001) and 0.79 (95% CI 0.62–0.91; P < 0.001), respectively.

A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62–0.90; P < 0.001) and 0.63 (95% CI 0.43–0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36–0.73; P < 0.001), and 0.26(95% CI 0.11–0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort.

Conclusions

Early OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group.

Graphical Abstract
SIRT1 prevents cigarette smoking-induced lung fibroblasts activation by regulating mitochondrial oxidative stress and lipid metabolism
Authors: Zhang Yue , Li Ting , Pan Miaoxia , Wang Wei , Huang Wenhui , Yuan Yafei , Xie Zhanzhan , Chen Yixin , Peng Jun , Li Xu , Meng Ying
Published: May 2022

Background

Cigarette smoking (CS) is a strong risk factor for idiopathic pulmonary fibrosis (IPF). It can activate lung fibroblasts (LF) by inducing redox imbalance. We previously showed that clearing mitochondrial reactive oxygen species (mtROS) protects against CS-induced pulmonary fibrosis. However, the precise mechanisms of mtROS in LF need further investigation. Here we focused on mtROS to elucidate how it was regulated by CS in LF and how it contributed to LF activation.

Methods

We treated cells with 1% cigarette smoking extract (CSE) and examined mtROS level by MitoSOX™ indicator. And the effect of CSE on expression of SIRT1, SOD2, mitochondrial NOX4 (mtNOX4), fatty acid oxidation (FAO)-related protein PPARα and CPT1a and LF activation marker Collagen I and α-SMA were detected. Nile Red staining was performed to show cellular lipid content. Then, lipid droplets, autophagosome and lysosome were marked by Bodipy 493/503, LC3 and LAMP1, respectively. And lipophagy was evaluated by the colocalization of lipid droplets with LC3 and LAMP1. The role of autophagy on lipid metabolism and LF activation were explored. Additionally, the effect of mitochondria-targeted ROS scavenger mitoquinone and SIRT1 activator SRT1720 on mitochondrial oxidative stress, autophagy flux, lipid metabolism and LF activation were investigated in vitro and in vivo.

Results

We found that CS promoted mtROS production by increasing mtNOX4 and decreasing SOD2. Next, we proved mtROS inhibited the expression of PPARα and CPT1a. It also reduced lipophagy and upregulated cellular lipid content, suggesting lipid metabolism was disturbed by CS. In addition, we showed both insufficient FAO and lipophagy resulted from blocked autophagy flux caused by mtROS. Moreover, we uncovered decreased SIRT1 was responsible for mitochondrial redox imbalance. Furthermore, we proved that both SRT1720 and mitoquinone counteracted the effect of CS on NOX4, SOD2, PPARα and CPT1a in vivo.

Conclusions

We demonstrated that CS decreased SIRT1 to activate LF through dysregulating lipid metabolism, which was due to increased mtROS and impaired autophagy flux. These events may serve as therapeutic targets for IPF patients.
RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma
Authors: Chen Shijie , Zeng Jin , Huang Liping , Peng Yi , Yan Zuyun , Zhang Aiqian , Zhao Xingping , Li Jun , Zhou Ziting , Wang Sidan , Jing Shengyu , Hu Minghua , Li Yuezhan , Wang Dong , Wang Weiguo , Yu Haiyang , Miao Jinglei , Li Jinsong , Deng Youwen , Li Yusheng , Liu Tang , Xu Dabao
Published: May 2022

Background

RNA adenosine modifications, which are primarily mediated by “writer” enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear.

Methods

Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS.

Results

A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase.

Conclusion

The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.
Heat shock protein A4 ablation leads to skeletal muscle myopathy associated with dysregulated autophagy and induced apoptosis
Authors: Elkenani Manar , Barakat Amal Z. , Held Torsten , Rodrigues Daniel Marques , Mobarak Sherok , Swarnka Surabhi , Adham Ibrahim M. , Mohamed Belal A.
Published: May 2022

Background

Molecular chaperones assist protein folding, facilitate degradation of misfolded polypeptides, and thereby maintain protein homeostasis. Impaired chaperone activity leads to defective protein quality control that is implicated in multiple skeletal muscle diseases. The heat shock protein A4 (HSPA4) acts as a co-chaperone for HSP70. Previously, we showed that Hspa4 deletion causes impaired protein homeostasis in the heart. However, its functional role in skeletal muscle has not been explored.

Methods

We performed a comparative phenotypic and biochemical analyses of Hspa4 knockout (KO) mice with wild-type (WT) littermates.

Results

HSPA4 is markedly upregulated in regenerating WT muscle in vivo, and in differentiated myoblasts in vitro. Hspa4-KO mice are marked by growth retardation and increased variability in body weight, accompanied by 35% mortality rates during the peri-weaning period. The surviving Hspa4-KO mice experienced progressive skeletal muscle myopathy, characterized by increased number of muscle fibers with centralized nuclei, heterogeneous myofiber size distribution, inflammatory cell infiltrates and upregulation of embryonic and perinatal myosin heavy chain transcripts. Hspa4-KO muscles demonstrated an accumulation of autophagosome-associated proteins including microtubule associated protein1 light chain 3-II (LC3-II) and p62/sequestosome accompanied by increased number of TUNEL-positive nuclei.

Conclusions

Our findings underscore the indispensable role of HSPA4 in maintenance of muscle integrity through contribution in skeletal muscle autophagy and apoptosis, which might provide a novel therapeutic strategy for skeletal muscle morbidities.
The progression rate of spinocerebellar ataxia type 3 varies with disease stage
Authors: Peng Linliu , Peng Yun , Chen Zhao , Wang Chunrong , Long Zhe , Peng Huirong , Shi Yuting , Shen Lu , Xia Kun , Leotti Vanessa B. , Jardim Laura Bannach , Tang Beisha , Qiu Rong , Jiang Hong
Published: May 2022

Background

In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions.

Methods

Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models.

Results

An acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available.

Conclusions

We first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp.
Incidence and immunomic features of apyretic COVID-19 in patients affected by solid tumors: a prospective cohort study
Authors: Ravera Francesco , Borea Roberto , Cirmena Gabriella , Dameri Martina , Ferrando Lorenzo , Gallo Maurizio , Casini Cecilia , Fallani Neri , Stabile Mario , Barbero Valentina , Murialdo Roberto , Tixi Lucia , Cappuccio Margherita , Cuboni Andrea , Sivieri Irene , Fornarini Giuseppe , De Maria Andrea , Ballestrero Alberto , Zoppoli Gabriele
Published: May 2022

Background and rationale

Little is known about SARS-CoV-2 seroconversion in asymptomatic patients affected by solid cancer, and whether it is associated with specific transcriptomics changes in peripheral blood mononuclear cells (PBMC).

Methods

Patients affected by solid cancer treated in a top comprehensive cancer center in Italy during the first COVID-19 pandemic wave, and negative for COVID-19-symptoms since the first detection of COVID-19 in Italy, were prospectively evaluated by SARS-CoV-2 serology in the period between April 14th and June 23rd 2020. Follow-up serologies were performed, every 21–28 days, until August 23rd 2020. All SARS-CoV-2 IgM + patients underwent confirmatory nasopharyngeal swab (NPS). PBMCs from a subset of SARS-CoV-2 IgM + patients were collected at baseline, at 2 months, and at 7 months for transcriptome sequencing.

Results

SARS-CoV-2 serology was performed on 446 of the 466 recruited patients. A total of 14 patients (3.14%) tested positive for at least one SARS-CoV-2 immunoglobulin in the period between April 14th and August 23rd 2020. Incidence of SARS-CoV-2 IgM decreased from 1.48% in the first month of the accrual to 0% in the last month. Viral RNA could not be detected in any of the NPS. PBMC serial transcriptomic analysis showed progressive downregulation of interleukin 6 upregulated signatures, chemokine-mediated signaling and chemokine-chemokine receptor KEGG pathways. B- and T-cell receptor pathways (p-values = 0.0002 and 0.017 respectively) were progressively upregulated.

Conclusions

SARS-CoV-2 seroconversion rate in asymptomatic patients affected by solid cancer is consistent with that of asymptomatic COVID-19 assessed in the general population through NPS at the peak of the first wave. Transcriptomic features over time in IgM + asymptomatic cases are suggestive of previous viral exposure.
High-fat diet exacerbates cognitive decline in mouse models of Alzheimer's disease and mixed dementia in a sex-dependent manner
Authors: Gannon Olivia J. , Robison Lisa S. , Salinero Abigail E. , Abi-Ghanem Charly , Mansour Febronia M. , Kelly Richard D. , Tyagi Alvira , Brawley Rebekah R. , Ogg Jordan D. , Zuloaga Kristen L.
Published: May 2022

Background

Approximately 70% of Alzheimer’s disease (AD) patients have co-morbid vascular contributions to cognitive impairment and dementia (VCID); this highly prevalent overlap of dementia subtypes is known as mixed dementia (MxD). AD is more prevalent in women, while VCID is slightly more prevalent in men. Sex differences in risk factors may contribute to sex differences in dementia subtypes. Unlike metabolically healthy women, diabetic women are more likely to develop VCID than diabetic men. Prediabetes is 3× more prevalent than diabetes and is linked to earlier onset of dementia in women, but not men. How prediabetes influences underlying pathology and cognitive outcomes across different dementia subtypes is unknown. To fill this gap in knowledge, we investigated the impact of diet-induced prediabetes and biological sex on cognitive function and neuropathology in mouse models of AD and MxD.

Methods

Male and female 3xTg-AD mice received a sham (AD model) or unilateral common carotid artery occlusion surgery to induce chronic cerebral hypoperfusion (MxD model). Mice were fed a control or high fat (HF; 60% fat) diet from 3 to 7 months of age. In both sexes, HF diet elicited a prediabetic phenotype (impaired glucose tolerance) and weight gain.

Results

In females, but not males, metabolic consequences of a HF diet were more severe in AD or MxD mice compared to WT. In both sexes, HF-fed AD or MxD mice displayed deficits in spatial memory in the Morris water maze (MWM). In females, but not males, HF-fed AD and MxD mice also displayed impaired spatial learning in the MWM. In females, but not males, AD or MxD caused deficits in activities of daily living, regardless of diet. Astrogliosis was more severe in AD and MxD females compared to males. Further, AD/MxD females had more amyloid beta plaques and hippocampal levels of insoluble amyloid beta 40 and 42 than AD/MxD males. In females, but not males, more severe glucose intolerance (prediabetes) was correlated with increased hippocampal microgliosis.

Conclusions

High-fat diet had a wider array of metabolic, cognitive, and neuropathological consequences in AD and MxD females compared to males. These findings shed light on potential underlying mechanisms by which prediabetes may lead to earlier dementia onset in women.
Breastfeeding and complementary feeding in fragile settings: the case of Syrian refugees and their host communities in North Lebanon
Authors: Daher Sara , Ziade Fouad , Nasreddine Lara , Baroudi Moomen , Naja Farah
Published: May 2022

Background

Adequate breastfeeding and complementary feeding practices are paramount in fragile situations where access to food and healthcare is limited. The objectives of this study are to examine breastfeeding and complementary feeding practices among Syrian refugees and their Lebanese host communities and to investigate the correlates of exclusive breastfeeding (EBF) at four and 6 months in these communities.

Methods

Using two-stage stratified sampling, a cross-sectional survey was conducted in Akkar, a region with a high density of Syrian refugees in Lebanon, between April and November 2019. In one-to-one interviews, mothers of children (6–24 months) completed a questionnaire including specific questions about breastfeeding and complementary feeding practices, a 24-h recall, and socio-demographic characteristics for 189 Syrian refugees and 182 Lebanese host community households. Descriptive statistics, simple and multiple logistic regression were used in data analysis.

Results

Among breastfeeding practices, ever-breastfeeding was most prevalent (90%), followed by early initiation of breastfeeding (64.8%), EBF at four (49.6%), and six (36%) months. One in four children was introduced to solids before 6 months of age, and less than a third was given iron-fortified baby cereals as the first complementary foods. Only 24.4% and 9.2% of children met the minimum dietary diversity and minimum acceptable diet requirements, respectively. Compared to children of the Lebanese host communities, those of Syrian refugees had higher rates of EBF at four and 6 months as well as continued breastfeeding at 1 year, whereas only 17.9% of Syrian refugees’ children met minimum dietary diversity compared to 30.9% of Lebanese host community children (p <  0.05). Among refugees, education and spouse’s employment status were associated with higher odds of EBF at 4 months. As for Lebanese households, female children were less likely to be exclusively breastfed at 4 months and 6 months, while a natural delivery increased the odds of EBF at 6 months.

Conclusion

Breastfeeding and complementary feeding practices are suboptimal among children of Syrian refugees and their Lebanese host communities in North Lebanon. There is a need for intervention strategies to tackle gaps in services and assistance delivery programs to enhance infant and young child feeding practices among both communities.
Safety considerations in the evolving legal landscape of psychedelic-assisted psychotherapy
Authors: Mocanu Victor , Mackay Lindsay , Christie Devon , Argento Elena
Published: May 2022

International drug policy is rapidly evolving in tandem with promising evidence for psychedelic-assisted psychotherapy (PAP) in treating a range of mental health conditions. Canada is among the countries increasingly expanding access to psychedelic substances for therapeutic purposes. The 8-year ban on medical exemptions through the Canadian Special Access Programme was recently reversed in January 2022 and the first exemptions for legal possession and personal use of psilocybin mushrooms were granted in 2020, nearly 50 years since their criminalization. In view of the evolving evidence base and regulatory landscape for PAP illustrated by recent shifts in Canadian and international drug policy, this piece seeks to clarify the special range of factors which ought to be considered to safely expand access to psychedelics. Streamlining access to safe and evidence-based compassionate use of PAP will provide a timely treatment option to those currently in need while encouraging further research and outcome surveillance to refine best practices.
Changes in hip joint contact stress during a gait cycle based on the individualized modeling method of “gait-musculoskeletal system-finite element”
Authors: Xiong Binglang , Yang Peng , Lin Tianye , Xu Jingli , Xie Yong , Guo Yongliang , Liu Churong , Zhou QIzhao , Lai Qizhong , He Wei , Wei Qiushi , Zhang Qingwen
Published: May 2022

Objective

To construct a comprehensive simulation method of “gait-musculoskeletal system (MS)-finite element (FE)” for analysis of hip joint dynamics characteristics and the changes in the contact stress in the hip throughout a gait cycle.

Methods

Two healthy volunteers (male and female) were recruited. The 3D gait trajectories during normal walking and the CT images including the hip and femur of the volunteers were obtained. CT imaging data in the DICOM format were extracted for subjected 3D hip joint reconstruction. The reconstructed 3D model files were used to realize the subject-specific registration of the pelvis and thigh segment of general musculoskeletal model. The captured marker trajectory data were used to drive subject-specific musculoskeletal model to complete inverse dynamic analysis. Results of inverse dynamic analysis were exported and applied as boundary and load settings of the hip joint finite element in ABAQUS. Finally, the finite element analysis (FEA) was performed to analyze contact stress of hip joint during a gait cycle of left foot.

Results

In the inverse dynamic analysis, the dynamic changes of the main hip-femoral muscle force with respect to each phase of a single gait cycle were plotted. The hip joint reaction force reached a maximum value of 2.9%BW (body weight) and appeared at the end of the terminal stance phase. Twin peaks appeared at the initial contact phase and the end of the terminal stance phase, respectively. FEA showed the temporal changes in contact stress in the acetabulum. In the visual stress cloud chart, the acetabular contact stress was mainly distributed in the dome of the acetabulum and in the anterolateral area at the top of the femoral head during a single gait cycle. The acetabular contact area was between 293.8 and 998.4 mm2, and the maximum contact area appear at the mid-stance phase or the loading response phase of gait. The maximum contact stress of the acetabulum reached 6.91 MPa for the model 1 and 6.92 MPa for the model 2 at the terminal stance phase.

Conclusions

The “Gait-MS-FE” technology is integrated to construct a comprehensive simulation framework. Based on human gait trajectories and their CT images, individualized simulation modeling can be achieved. Subject-specific gait in combination with an inverse dynamic analysis of the MS provides pre-processing parameters for FE simulation for more accurate biomechanical analysis of hip joint.

Graphical abstract
Biomechanical study of oblique lumbar interbody fusion (OLIF) augmented with different types of instrumentation: a finite element analysis
Authors: Cai Xin-Yi , Bian Han-Ming , Chen Chao , Ma Xin-Long , Yang Qiang
Published: May 2022

Background

To explore the biomechanical differences in oblique lumbar interbody fusion (OLIF) augmented by different types of instrumentation.

Methods

A three-dimensional nonlinear finite element (FE) model of an intact L3-S1 lumbar spine was built and validated. The intact model was modified to develop five OLIF surgery models (Stand-alone OLIF; OLIF with lateral plate fixation [OLIF + LPF]; OLIF with unilateral pedicle screws fixation [OLIF + UPSF]; OLIF with bilateral pedicle screws fixation [OLIF + BPSF]; OLIF with translaminar facet joint fixation + unilateral pedicle screws fixation [OLIF + TFJF + UPSF]) in which the surgical segment was L4–L5. Under a follower load of 500 N, a 7.5-Nm moment was applied to all lumbar spine models to calculate the range of motion (ROM), equivalent stress peak of fixation instruments (ESPFI), equivalent stress peak of cage (ESPC), equivalent stress peak of cortical endplate (ESPCE), and equivalent stress average value of cancellous bone (ESAVCB).

Results

Compared with the intact model, the ROM of the L4–L5 segment in each OLIF surgery model decreased by > 80%. The ROM values of adjacent segments were not significantly different. The ESPFI, ESPC, and ESPCE values of the OLIF + BPSF model were smaller than those of the other OLIF surgery models. The ESAVCB value of the normal lumbar model was less than the ESAVCB values of all OLIF surgical models. In most postures, the ESPFI, ESPCE, and ESAVCB values of the OLIF + LPF model were the largest. The ESPC was higher in the Stand-alone OLIF model than in the other OLIF models. The stresses of several important components of the OLIF + UPSF and OLIF + TFJF + UPSF models were between those of the OLIF + LPF and OLIF + BPSF models.

Conclusions

Our biomechanical FE analysis indicated the greater ability of OLIF + BPSF to retain lumbar stability, resist cage subsidence, and maintain disc height. Therefore, in the augmentation of OLIF, bilateral pedicle screws fixation may be the best approach.
Proximal junctional fractures after long-segment instrumented fusion: comparisons between upper instrumented vertebrae and upper instrumented vertebrae + 1
Authors: Liao Jen-Chung , Chen Wen-Jer , Wu Shiny Chih-Hsuan
Published: May 2022

Introduction

Proximal junctional failure (PJF) is a well-known complication after long-segment (at least 4 vertebral levels) instrumented fusion. The etiologies of PJF include degenerative processes or are fracture induced. The fracture type of PJF includes vertebral fractures developed at the upper instrumented vertebrae (UIV) or UIV + 1. The purpose of this study was to investigate clinical and radiographic features of these two subtypes of PJF and to analyze risk factors in these patients.

Method

In total, forty-two patients with PJF who underwent revision surgery were included. Twenty patients suffered fractures at the UIV, and the other 22 cases had fractures at UIV + 1. The weighted Charlson Comorbidity Index (CCI) and bone mineral density (BMD) T scores for these patients were recorded. Surgery-related data of index surgery and complications were collected. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), lumbar lordosis (LL), and PI-LL were recorded in both groups before and after the revision surgery.

Result

Both groups had severe osteoporosis and comorbidities. The interval between the index surgery and revision surgery was shorter in the UIV group than in the UIV + 1 group (8.2 months vs. 35.9 months; p < 0.001). The analysis for radiographic parameters in UIV and UIV + 1 group demonstrated no significant change before and after the revision surgery. However, the preoperative radiographic analysis showed a larger PT (31.5° vs. 23.2°, p = 0.013), PI (53.7° vs. 45.3°, p = 0.035), and SVA (78.6° vs. 59.4°, p = 0.024) in the UIV group compared to the UIV + 1 group. The postoperative radiographic analysis showed a larger PI-LL (27.8° vs. 18.1°, p = 0.016) in the UIV group compared to the UIV + 1 group.

Conclusion

PJF in the UIV group tends to occur earlier than in the UIV + 1 group. Moreover, more severe global sagittal imbalances were found in the UIV group than in UIV + 1 group.
MiR-144-3p inhibits the proliferation and metastasis of lung cancer A549 cells via targeting HGF
Authors: Fang Guiju , Zhang Canhui , Liu Zhixin , Peng Zhiwen , Tang Meiyan , Xue Qing
Published: May 2022

Aim

MicroRNAs have been confirmed as vital regulators in gene expression, which could affect multiple cancer cell biological behaviors. This study aims to elucidate the molecular mechanism of miR-144-3p in lung cancer cellular proliferation and metastasis.

Methods

MiR-144-3p expression in lung cancer tissues and cell lines was detected by qRT-PCR. HGF was predicted as the target gene of miR-144-3p using TargetScan and dual luciferase reporter assay. Immunohistochemistry and qRT-PCR were used to explore the impacts of HCF on lung cancer tissues and cell lines. Impacts of miR-144-3p and HGF on cancer cellular proliferation, migration and invasion were elucidated by CCK-8, Flow cytometry, Transwell invasion and Wound-healing assay. Moreover, nude mouse xenograft model was established to evaluate the effects of miR-144-3p on lung cancer cells.

Results

MiR-144-3p exhibited a reduction in both lung cancer tissues and cell lines. HGF was a direct target of miR-144-3p. In contrast to the miR-144-3p expression level, HGF showed a higher level in lung cancer tissues and cell lines. Overexpression miR-144-3p suppressed A549 and NCI-H1299 cell proliferation and metastasis, whereas this was reversed by HGF. MiR-144-3p exhibited an inhibitory effect on A549 cell-induced tumor growth of nude mice.

Conclusions

This study reveals miR-144-3p/HGF axis may be involved in the suppression of lung cancer cellular proliferation and development, and miR-144-3p may function as a potential therapeutic target in lung cancer treatment in the future.
Preventing suicide in refugees and asylum seekers: a rapid literature review examining the role of suicide prevention training for health and support staff
Authors: Ingram Jessica , Lyford Bronte , McAtamney Amanda , Fitzpatrick Sally
Published: May 2022

Background

Refugees and asylum seekers are exposed to a unique set of circumstances and experiences that are associated with an increased suicide risk. Suicide prevention training has been recognised as a central component supporting a comprehensive approach to suicide prevention. Limited literature exists exploring the role of suicide prevention training for health and support staff working with refugee and asylum seeker consumers.

Methods

To determine the impact suicide prevention training for health staff may have in supporting refugee and asylum seeker suicide prevention, researchers undertook a rapid literature review exploring what elements should be considered when developing suicide prevention training for health and support staff working with refugee and asylum seeker consumers.

Results

Results of academic and grey literature screening identified 14 studies exploring suicide prevention training for health and support staff working with refugee and asylum seeker consumers. Findings of the literature review suggest suicide prevention training for health and support staff working with refugee and asylum seekers should consider the inclusion of content which increases participant competence and confidence to identify and respond to suicide risk; provide staff with an understanding of cultural differences and its impact on refugees and asylum seekers recognition of mental health and suicide as a health matter; highlight the importance trauma informed practices in care and consider the lived experience of refugees and asylum seekers.

Conclusions

Inclusion of specific content in refugee and asylum seeker suicide prevention training may provide health and support staff increased competence and confidence to identify and respond to suicide risk in refugees and asylum seekers.
The enhancer RNA ADCY10P1 is associated with the progression of ovarian cancer
Authors: Mo Jiaya , Zhang Lianghao , Li Huiqing , Duan Haoran , Wang Dong , Zhao Xiaolei , Xie Ya
Published: May 2022

Background

Emerging evidence identifies enhancer RNAs (eRNAs) as a class of regulatory ncRNAs that can contribute to the transcription of target genes. In this study, we used an integrated data analysis method to identify the important role of eRNAs in ovarian cancer (OC).

Methods

Gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) database were used for this study. Based on expression analysis using GEPIA2 gene and Kaplan–Meier survival was performed to ensure the significance of the selected enhancer RNA ADCY10P1 in OC. Next, we explored the correlation and clinical significance between ADCY10P1 and target gene NFYA. Furthermore, we evaluated the effects of overexpression of ADCY10P1 on the proliferation, migration, invasion and epithelial-mesenchymal transformation (EMT) of OC cell lines. We also investigated the biological function enrichment score of ADCY10P1 and verified it with OC cell lines. Finally, external validation was conducted, and the prognostic value of the ADCY10P1 in different tumors was demonstrated.

Results

We selected the eRNA ADCY10P1 associated with OC prognosis, with NFYA as its predicted target gene. Low ADCY10P1 expression was found to be associated with poor overall survival, high histological grade, and advanced stage of OC. Additionally, overexpression of ADCY10P1 inhibited the proliferation, migration, invasion and EMT phenotype of OC cell lines. Furthermore, ADCY10P1 was observed to inhibit glycolysis and fatty acid metabolism, thereby affecting OC progression. Meanwhile, OC tissue samples were externally validated. In addition, the pan-cancer analysis revealed that ADCY10P1 had prognostic value in other cancers.

Conclusions

This study showed that ADCY10P1 plays a key role in OC progression and may facilitate prognosis prediction.
Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy
Authors: Masini Marzio , Brindisi Giulia , Giovannini Mattia , Pignataro Elia , Di Grande Laura , De Libero Cinzia , Nebbioso Marcella , Mori Francesca , Caputo Roberto , Zicari Anna Maria
Published: May 2022

Background

The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown.

Methods

We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children’s University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure.

Results

Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure.

Conclusion

During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.
Response surface optimization of a vortex-assisted dispersive liquid–liquid microextraction method for highly sensitive determination of repaglinide in environmental water by HPLC/UV
Authors: Kamal Amira H. , Hammad Mohamed A. , Kannouma Reham E. , Mansour Fotouh R.
Published: May 2022

A vortex-assisted dispersive liquid–liquid microextraction (DLLME) method, mated to chemometrics and combined with HPLC/UV detection was optimized and validated for enrichment and determination of repaglinide in environmental samples using nateglinide as an internal standard (IS). A phosphate buffer (10 mM, pH 2.5): acetonitrile (45:55, v/v) was used as a mobile phase with a flow rate of 1 mL/min in an isocratic elution mode. Chemometrics-assisted optimization was performed using a quadratic integrated d-optimal design. The developed model assessed the statistical significance of the independent variables and their interactions to attain the optimum conditions revealing that extractant type, extractant volume and pH are the most influential factors. Optimization of the extraction procedures was performed with the aid of Design Expert 8® software, which suggested 58 different experiments. The optimal conditions were 30 µL of 1-octanol as extractant, 100 µL of acetonitrile as a disperser at pH 8. Under the optimized conditions, the method showed linearity over the range of 1–100 ng/mL with a limit of detection of 0.4 ng/mL. The accuracy, the intra- and inter-day precision were assessed, the %recoveries were found to be between 98.48 and 100.81% with %RSD lower than 1.3. Using chemometrics in method optimization helped achieve the maximum possible enrichment with the least effort, time, and reagents while considering all possible interactions between variables.
Microfluidic screening and genomic mutation identification for enhancing cellulase production in Pichia pastoris
Authors: Yuan Huiling , Zhou Ying , Lin Yuping , Tu Ran , Guo Yufeng , Zhang Yuanyuan , Wang Qinhong
Published: May 2022

Background

Pichia pastoris is a widely used host organism for heterologous production of industrial proteins, such as cellulases. Although great progress has been achieved in improving protein expression in P. pastoris, the potential of the P. pastoris expression system has not been fully explored due to unknown genomic impact factors. Recently, whole-cell directed evolution, employing iterative rounds of genome-wide diversity generation and high-throughput screening (HTS), has been considered to be a promising strategy in strain improvement at the genome level.

Results

In this study, whole-cell directed evolution of P. pastoris, employing atmospheric and room temperature plasma (ARTP) mutagenesis and droplet-based microfluidic HTS, was developed to improve heterogenous cellulase production. The droplet-based microfluidic platform based on a cellulase-catalyzed reaction of releasing fluorescence was established to be suitable for methanol-grown P. pastoris. The validation experiment showed a positive sorting efficiency of 94.4% at a sorting rate of 300 droplets per second. After five rounds of iterative ARTP mutagenesis and microfluidic screening, the best mutant strain was obtained and exhibited the cellulase activity of 11,110 ± 523 U/mL, an approximately twofold increase compared to the starting strain. Whole-genome resequencing analysis further uncovered three accumulated genomic alterations in coding region. The effects of point mutations and mutant genes on cellulase production were verified using reconstruction of point mutations and gene deletions. Intriguingly, the point mutation Rsc1G22V was observed in all the top-performing producers selected from each round, and gene deletion analysis confirmed that Rsc1, a component of the RSC chromatin remodeling complex, might play an important role in cellulase production.

Conclusions

We established a droplet-based microfluidic HTS system, thereby facilitating whole-cell directed evolution of P. pastoris for enhancing cellulase production, and meanwhile identified genomic alterations by whole-genome resequencing and genetic validation. Our approaches and findings would provide guides to accelerate whole-cell directed evolution of host strains and enzymes of high industrial interest.