bluuebunny/crossref_metadata_2025 huggingface dataset:
How an emergency department is organized to provide opioid-specific harm reduction and facilitators and barriers to harm reduction implementation: a systems perspective
Authors: Jiao Sunny , Bungay Vicky , Jenkins Emily , Gagnon Marilou
Published: September 2023

Background

The intersection of dual public health emergencies—the COVID-19 pandemic and the drug toxicity crisis—has led to an urgent need for acute care based harm reduction for unregulated opioid use. Emergency Departments (EDs) as Complex Adaptive Systems (CASs) with multiple, interdependent, and interacting elements are suited to deliver such interventions. This paper examines how the ED is organized to provide harm reduction and identifies facilitators and barriers to implementation in light of interactions between system elements.

Methods

Using a case study design, we conducted interviews with Emergency Physicians (n = 5), Emergency Nurses (n = 10), and clinical leaders (n = 5). Nine organizational policy documents were also collected. Interview data were analysed using a Reflexive Thematic Analysis approach. Policy documents were analysed using a predetermined coding structure pertaining to staffing roles and responsibilities and the interrelationships therein for the delivery of opioid-specific harm reduction in the ED. The theory of CAS informed data analysis.

Results

An array of system agents, including substance use specialist providers and non-specialist providers, interacted in ways that enable the provision of harm reduction interventions in the ED, including opioid agonist treatment, supervised consumption, and withdrawal management. However, limited access to specialist providers, when coupled with specialist control, non-specialist reliance, and concerns related to safety, created tensions in the system that hinder harm reduction provision with resulting implications for the delivery of care.

Conclusions

To advance harm reduction implementation, there is a need for substance use specialist services that are congruent with the 24 h a day service delivery model of the ED, and for organizational policies that are attentive to discourses of specialized practice, hierarchical relations of power, and the dynamic regulatory landscape. Implementation efforts that take into consideration these perspectives have the potential to reduce harms experienced by people who use unregulated opioids, not only through overdose prevention and improving access to safer opioid alternatives, but also through supporting people to complete their unique care journeys.
Caprini risk assessment model combined with D-dimer to predict the occurrence of deep vein thrombosis and guide intervention after laparoscopic radical resection of colorectal cancer
Authors: Zhang Wuming , Sun Ruizheng , Hu Xianqin , Chen Zhikang , Lai Chen
Published: September 2023

Background

To explore the diagnostic value of Caprini risk assessment model (2005) combined with D-dimer for deep vein thrombosis, and to exclude patients with low incidence of thrombosis who might not need anticoagulation after surgery.

Methods

A total of 171 colorectal cancer patients who underwent surgery from January 2022 to August 2022 were enrolled in this study. Caprini risk assessment model was used to evaluate patients the day before surgery, and full-length venous ultrasonography of lower extremity was used to assess whether patients had thrombosis one day before surgery and the sixth day after surgery. The value of D-dimer was measured by enzyme-linked immunosorbent assays on the first day after surgery, and clinical data of patients were collected during hospitalization.

Results

A total of 171 patients were divided into IPC Group and IPC + LMWH Group according to whether low molecular weight heparin (LMWH) were used to prevent thrombus after surgery. Eventually, 17.6% (15/85) patients in IPC Group and 7% (6/86) patients in IPC + LMWH Group developed DVT. Through separate analysis of IPC Group, it is found that Caprini score and D-dimer were independent risk factors for DVT (Caprini OR 3.39 [95% CI 1.38–8.32]; P = 0.008, D-Dimer OR 6.142 [95% CI 1.209–31.187]; P = 0.029). The area under ROC curve of Caprini risk assessment model is 0.792 (95% CI 0.69–0.945, P < 0.01), the cut-off value is 9.5, and the area under ROC curve of D-dimer is 0.738 (95%CI 0.555–0.921, P < 0.01), the cut-off value is 0.835 μg/mL, and the area under the ROC curve was 0.865 (95% CI 0.754–0.976, P < 0.01) when both of them were combined. Based on decision curve analysis, it is found that Caprini risk assessment model combined with D-dimer can benefit patients more. All patients are divided into four groups. When Caprini score < 10 and D-dimer < 0.835 μg/mL, only 1.23% (1/81) of patients have thrombosis and LMWH has little significance. When Caprini score > 10 and D-dimer > 0.835 μg/mL, the incidence of DVT is 38.7% (12/31) and LMWH should be considered.

Conclusions

The Caprini risk assessment model and D-dimer can provide more accurate risk stratification for patients after laparoscopic radical resection of colorectal cancer.
Fasting-mimicking diet alleviates inflammatory pain by inhibiting neutrophil extracellular traps formation and neuroinflammation in the spinal cord
Authors: Li Ting , Yue Ying , Ma Yan , Zhong Ziwen , Guo Miaomiao , Zhang Jie , Wang Zhiping , Miao Changhong
Published: September 2023

Background

Neutrophil extracellular traps (NETs) promote neuroinflammation and, thus, central nervous system (CNS) disease progression. However, it remains unclear whether CNS-associated NETs affect pain outcomes. A fasting-mimicking diet (FMD) alleviates neurological disorders by attenuating neuroinflammation and promoting nerve regeneration. Hence, in this study, we explore the role of NETs in the CNS during acute pain and investigate the role of FMD in inhibiting NETs and relieving pain.

Methods

The inflammatory pain model was established by injecting complete Freund’s adjuvant (CFA) into the hind paw of mice. The FMD diet regimen was performed during the perioperative period. PAD4 siRNA or CI-amidine (PAD4 inhibitor) was used to inhibit the formation of NETs. Monoamine oxidase-B (MAO-B) knockdown occurred by AAV-GFAP-shRNA or AAV-hSyn-shRNA or was inhibited by selegiline (an MAO-B inhibitor). The changes in NETs, neuroinflammation, and related signaling pathways were examined by western blot, immunofluorescence, ELISA, and flow cytometry.

Results

In the acute phase of inflammatory pain, NETs accumulate in the spinal cords of mice. This is associated with exacerbated neuroinflammation. Meanwhile, inhibition of NETs formation alleviates allodynia and neuroinflammation in CFA mice. FMD inhibits NETs production and alleviates inflammatory pain, which is enhanced by treatment with the NETs inhibitor CI-amidine, and reversed by treatment with the NETs inducer phorbol 12-myristate 13-acetate (PMA). Mechanistically, the neutrophil-recruiting pathway MAO-B/5-hydroxyindoleacetic acid (5-HIAA) / G-protein-coupled receptor 35 (GPR35) and NETs-inducing pathway MAO-B/ Reactive oxygen species (ROS) are significantly upregulated during the development of inflammatory pain. MAO-B is largely expressed in astrocytes and neurons in the spinal cords of CFA mice. However, knockdown or inhibition of MAO-B effectively attenuates CFA-induced inflammatory pain, NETs formation, and neuroinflammation in the spinal cord. Moreover, within rescue experiments, MAO-B inhibitors synergistically enhance FMD-induced pain relief, NETs inhibition, and neuroinflammation attenuation, whereas supplementation with MAO-B downstream molecules (i.e., 5-HIAA and PMA) abolished this effect.

Conclusions

Neutrophil-released NETs in the spinal cord contribute to pain development. FMD inhibits NETs formation and NETs-induced neuroinflammation by inhibiting the MAO-B/5-HIAA/GPR35 and MAO-B/ROS pathways in astrocytes and neurons, thereby relieving pain progression.
Going beyond PA: Assessing sensorimotor capacity with wearables in multiple sclerosis—a cross-sectional study
Authors: Gulde Philipp , Vojta Heike , Schmidle Stephanie , Rieckmann Peter , Hermsdörfer Joachim
Published: September 2023

Background

Wearable technologies are currently clinically used to assess energy expenditure in a variety of populations, e.g., persons with multiple sclerosis or frail elderly. To date, going beyond physical activity, deriving sensorimotor capacity instead of energy expenditure, is still lacking proof of feasibility.

Methods

In this study, we read out sensors (accelerometer and gyroscope) of smartwatches in a sample of 90 persons with multiple sclerosis over the course of one day of everyday life in an inpatient setting. We derived a variety of different kinematic parameters, in addition to lab-based tests of sensorimotor performance, to examine their interrelation by principal component, cluster, and regression analyses.

Results

These analyses revealed three components of behavior and sensorimotor capacity, namely clinical characteristics with an emphasis on gait, gait-related physical activity, and upper-limb related physical activity. Further, we were able to derive four clusters with different behavioral/capacity patterns in these dimensions. In a last step, regression analyses revealed that three selected smartwatch derived kinematic parameters were able to partially predict sensorimotor capacity, e.g., grip strength and upper-limb tapping.

Conclusions

Our analyses revealed that physical activity can significantly differ between persons with comparable clinical characteristics and that assessments of physical activity solely relying on gait can be misleading. Further, we were able to extract parameters that partially go beyond physical activity, with the potential to be used to monitor the course of disease progression and rehabilitation, or to early identify persons at risk or a sub-clinical threshold of disease severity.
Strategies for enacting health policy codesign: a scoping review and direction for research
Authors: Walker Sarah Cusworth , Baquero Barbara , Bekemeier Betty , Parnes McKenna , Arora Kashika
Published: September 2023

Background

Strategies for supporting evidence-informed health policy are a recognized but understudied area of policy dissemination and implementation science. Codesign describes a set of strategies potentially well suited to address the complexity presented by policy formation and implementation. We examine the health policy literature describing the use of codesign in initiatives intended to combine diverse sources of knowledge and evidence in policymaking.

Methods

The search included PubMed, MEDLINE, PsychInfo, CINAHL, Web of Science, and Google Scholar in November 2022 and included papers published between 1996 and 2022. Terms included codesign, health, policy, and system terminology. Title and abstracts were reviewed in duplicate and included if efforts informed policy or system-level decision-making. Extracted data followed scoping review guidelines for location, evaluation method, health focus, codesign definition, description, level of health system user input, sectors involved, and reported benefits and challenges.

Results

From 550 titles, 23 citations describing 32 policy codesign studies were included from multiple continents (Australia/New Zealand, 32%; UK/Europe, 32%; South America, 14%; Africa, 9%; USA/Canada 23%). Document type was primarily case study (77%). The area of health focus was widely distributed. Policy type was more commonly little p policy (47%), followed by big p policy (25%), and service innovations that included policy-enabled funding (25%). Models and frameworks originated from formal design (e.g., human-centered or participatory design (44%), political science (38%), or health service research (16%). Reported outcomes included community mobilization (50%), policy feasibility (41%), improved multisector alignment (31%), and introduction of novel ideas and critical thinking (47%). Studies engaging policy users in full decision-making roles self-reported higher levels of community mobilization and community needs than other types of engagement.

Discussion

Policy codesign is theoretically promising and is gaining interest among diverse health sectors for addressing the complexity of policy formation and implementation. The maturity of the science is just emerging. We observed trends in the association of codesign strategies and outcomes that suggests a research agenda in this area could provide practical insights for tailoring policy codesign to respond to local contextual factors including values, needs, and resources.
Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers
Authors: Liu Chi-Hung , Lin Chien-Yu , Huang Bing-Shen , Wei Yi-Chia , Chang Ting-Yu , Yeh Chih-Hua , Sung Pi-Shan , Jiang Jian-Lin , Lin Li-Ying , Chang Joseph Tung-Chieh , Fan Kang-Hsing
Published: September 2023

Background

To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods.

Methods

We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan–Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC.

Results

Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%,  p < 0.01) and were more commonly associated with TLN in the Kaplan–Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37–130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan–Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70).

Conclusion

Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.
DAP1 regulates osteoblast autophagy via the ATG16L1–LC3 axis in Graves’ disease-induced osteoporosis
Authors: Gao Mingdong , Du Zouxi , Dong Qianqian , Su Shan , Tian Limin
Published: September 2023

Objective

This study aimed to uncover a critical protein and its mechanisms in modulating autophagy in Graves’ disease (GD)-induced osteoporosis (OP).

Methods

We discovered the target protein, death-associated protein 1 (DAP1), using bone proteomics analysis. Furthermore, genetic overexpression and knockdown (KD) of DAP1 in bone and MC3T3-E1 cells revealed DAP1 effects on autophagy and osteogenic markers, and autophagic vacuoles in cells were detected using transmission electron microscopy and the microtubule-associated protein 1 light chain 3 alpha (MAP1LC3/LC3) dual fluorescence system. An autophagy polymerase chain reaction (PCR) array kit was used to identify the key molecules associated with DAP1-regulated autophagy.

Results

DAP1 levels were significantly higher in the bone tissue of GD mice and MC3T3-E1 cells treated with triiodothyronine (T3). DAP1 overexpression reduced LC3 lipidation, autophagic vacuoles, RUNX family transcription factor 2 (RUNX2), and osteocalcin (OCN) expression in MC3T3-E1 cells, whereas DAP1 KD reversed these changes. In vivo experiments revealed that GD mice with DAP1 KD had greater bone mass than control mice. DAP1-overexpressing (OE) cells had lower levels of phosphorylated autophagy-related 16-like 1 (ATG16L1) and LC3 lipidation, whereas DAP1-KD cells had higher levels.

Conclusions

DAP1 was found to be a critical regulator of autophagy homeostasis in GD mouse bone tissue and T3-treated osteoblasts because it negatively regulated autophagy and osteogenesis in osteoblasts via the ATG16L1–LC3 axis.
A systematic review on gender dysphoria in adolescents and young adults: focus on suicidal and self-harming ideation and behaviours
Authors: Marconi Elisa , Monti Laura , Marfoli Angelica , Kotzalidis Georgios D. , Janiri Delfina , Cianfriglia Cecilia , Moriconi Federica , Costa Stefano , Veredice Chiara , Sani Gabriele , Chieffo Daniela Pia Rosaria
Published: September 2023

Introduction

Gender dysphoria (GD) is characterized by the incongruence between one’s experienced and expressed gender and assigned-sex-at-birth; it is associated with clinically significant distress. In recent years, the number of young patients diagnosed with GD has increased considerably. Recent studies reported that GD adolescents present behavioural and emotional problems and internalizing problems. Furthermore, this population shows a prevalence of psychiatric symptoms, like depression and anxiety. Several studies showed high rates of suicidal and non-suicidal self-injurious thoughts and behaviour in GD adolescents. To increase understanding of overall mental health status and potential risks of young people with GD, this systematic review focused on risk of suicide and self-harm gestures.

Methods

We followed the PRISMA 2020 statement, collecting empirical studies from four electronic databases, i.e., PubMed, Scopus, PsycINFO, and Web of Science.

Results

Twenty-one studies on GD and gender nonconforming identity, suicidality, and self-harm in adolescents and young adults met inclusion criteria. Results showed that GD adolescents have more suicidal ideation, life-threatening behaviour, self-injurious thoughts or self-harm than their cisgender peers. Assessment methods were heterogeneous.

Conclusion

A standardised assessment is needed. Understanding the mental health status of transgender young people could help develop and provide effective clinical pathways and interventions.
HPLC/UV approach method for the first simultaneous estimation of molnupiravir and ertapenem as a binary mixture in human plasma and dosage form as a regimen for COVID-19 treatments
Authors: Afify Khaled K. , Ali Ramadan , El-Dosoky Mohammad A. , Nassar Mohamed wafaa I.
Published: September 2023

COVID-19 is a serious virus that can have a lot of effects, one of which is a secondary bacterial infection that can be more life-threatening and even lethal than the initial viral infection. Hence a fast and sensitive HPLC/UV method was developed and validated for the first estimation of a binary mixture of molnupiravir (MOL) and ertapenem (ERT) as a co-administrated medicine for the management of COVID-19 in pharmaceutical dosage forms, and human plasma samples. The drug combination was separated within 5 min via RP-ODS column using isocratic elution with a mobile phase of 0.05 M phosphate buffer (pH 3.5): acetonitrile with a 76: 24% ratio v/v. The presented method provided a linear response ranging from 0.03 to 17.0 and 0.05–20 µg mL−1 with LOD values of 0.009 and 0.008 µg mL−1 for MOL and ERT respectively. The good separation and high sensitivity of the HPLC method provide the determination of the cited drugs in human plasma without matrix interference with a percent of recovery ranging from 94.97 ± 2.05 to 98.44 ± 1.92. Based on the results, this method could be utilized to monitor cited drugs in quality control and therapeutic laboratories.
Green extraction of phenolics and flavonoids from black mulberry fruit using natural deep eutectic solvents: optimization and surface morphology
Authors: Vo Tan Phat , Pham Thuy Vy , Weina Kasia , Tran Thi Ngoc Huyen , Vo Le Thao Vy , Nguyen Phuc Thanh , Bui Tran Linh Ha , Phan Thuy Han , Nguyen Dinh Quan
Published: September 2023

This study deployed ultrasonic-assisted extraction (UAE), combined with natural deep eutectic solvents (NADES), to extract phenolics and flavonoids from the black mulberry fruit, and the antioxidant activity was examined. The extraction yields of NADES-based UAE were assessed based on the yields of phenolics and flavonoids extracted from the black mulberry fruit. This study selected the molar ratios of hydrogen bond acceptors (HBA) and hydrogen bond donors HBD at 1:2 from previous studies. Choline chloride-lactic acid showed the highest solubility with phenolics and flavonoids among NADES systems. One-factor experiments evaluated the effect of UAE conditions (liquid-to-solid ratio (LSR), water content in NADES, temperature, and time) on TPC, TFC, and antioxidant activity. The suitable NADES-based UAE conditions for extracting phenolics and flavonoids from the black mulberry fruit were 60 ml/g of LSR, 40% water content, 70 °C, and 15 min. Response surface methodology with the Box-Behnken design model optimized the NADES-based UAE process based on response (TPC, TFC, ABTS, OH, and DPPH). The optimal conditions for the NADES-based UAE process were 70 ml/g of LSR, 38.9% water content in NADES, 67.9 °C, and 24.2 min of extraction time. The predicted values of the Box-Behnken design were compatible with the experimental results. Moreover, scanning electron microscopy (SEM) was used to survey the surface of black mulberry fruit with and without sonication. SEM can assist in demonstrating the destructive effect of NADES and ultrasonic waves on material surfaces. SEM findings indicated the high surface destruction capacity of NADES, which partially contributed to a superior extraction yield of NADES than conventional organic solvents. The study proposes an efficient and green method for extracting bioactive compounds from black mulberry fruits. The black mulberry fruit extracts can be applied to meat preservation and beverages with high antioxidants.
Pharmacokinetics of fluralaner as a systemic drug to control infestations of the common bed bug, Cimex lectularius, in poultry facilities
Authors: González-Morales Maria A. , Thomson Andrea E. , Yeatts James , Enomoto Hiroko , Haija Ahmed , Santangelo Richard G. , Petritz Olivia A. , Crespo Rocio , Schal Coby , Baynes Ronald
Published: September 2023

Background

Bed bug infestations are re-emerging in the poultry industry throughout the USA. Although the impacts of bed bugs on birds’ health and welfare are poorly understood, adverse outcomes are expected, including stress, anemia, infections and lower production rates. Worker welfare is also an important consideration in commercial poultry farms. A limited number of insecticides are available for use in the complex spatial environment of commercial farms. Systemic drugs have the potential to overcome the limitations of existing pest management tactics. A recent study showed that fluralaner administered to chickens caused high levels of mortality in bed bugs.

Methods

To further understand the efficacy of this approach, we evaluated the pharmacokinetics of an oral solid formulation of fluralaner in 11 chickens and quantified its plasma concentration in chickens using UPLC/MS. We administered fluralaner to chickens with two doses of Bravecto® (each 0.5 mg/kg body mass) via gavage 1 week apart and evaluated its efficacy on bed bugs that fed on medicated chickens for up to 28 days post-treatment.

Results

Bed bugs that fed on fluralaner-treated chickens experienced > 50% mortality within 30 min of the administration of Bravecto and 100% mortality 2 days post-treatment. Mortality slowly declined to 66.6% by day 28. Fluralaner was quantifiable in the hens’ plasma for at least 28 days post-treatment. The treatment resulted in maximal plasma concentrations (Cmax) of 106.4 ng/ml around day 9.0 (Tmax), substantially higher than the LC90, the concentration needed to kill 90% of the bed bugs.

Conclusions

Fluralaner appears to be a promising candidate for bed bug control in poultry farms, with a treatment effect lasting at least 28 days.

Graphical Abstract
Unleashing potential and optimizing adolescent roller skating performance through a structured exercise program – a randomized controlled trial
Authors: Sehgal Sonakshi , Chahal Aksh , Esht Vandana , Alshehri Mohammed M. , Beg Rashid Ali , Shaphe Mohammad Abu , Alajam Ramzi Abdu , Kashoo Faizan Z. , Alghadir Ahmad H. , Khan Masood
Published: September 2023

Background

The intricate nature of an athlete's abilities evolves dynamically with the enhancement of motor skills. Hence the study sought to investigate the impact of a tailored four-week exercise program`encompassing exercises focused on balance, agility, and speed. The primary objective was to determine how this exercise program influences both the roller skating talent and overall physical fitness proficiency in young male roller skaters.

Methods

Thirty male participants (age 11–14 years) enrolled in the school skating team were recruited. The participants were randomized into either an experimental group [n = 15], performing a short-term exercise program, or a control group [n = 15], involved in the physical education classes for eight sessions over four weeks. The primary outcome measure, the skating performance, was measured by the linear speed test (LST). The secondary outcomes, i.e., balance, agility, and speed, were evaluated using the star excursion balance test (SEBT), agility t-test (ATT), and arrowhead change of direction speed test (ACDT). SEBT was assessed in 8 directions. The study was registered with the Clinical Trials Registry India (TRN: CTRI/2018/09/015713) before the recruitment of the participants on 14/09/2018.

Results

The results showed that LST, ATT, and ACDT improved significantly (p < 0.05) in both groups, however, greater (p < 0.05) improvement was observed in the experimental group (Cohen’s d 0.8 to 1.3). Regarding SEBT, improvement was observed in a few directions only in both groups. However, no significant difference was observed between both groups in SEBT measurements.

Conclusions

A short-term structured exercise program consisting of balance, agility, and speed exercises significantly improved the talent of skating, agility, and speed compared to physical education classes activities in young male roller skaters. The study highlights the potential of targeted training interventions to enhance athletic performance in this population.
Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study
Authors: Shakibay Senobari Zahra , Masoumian Hosseini Mohsen , Teimouri Mohammad Bagher , Rezayan Ali Hossein , Samarghandian Saeed , Hekmat Azadeh
Published: September 2023

Background

COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives’ ability to inhibit viral entry and prevent replication.

Method

This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa’s rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability.

Result

The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein–ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of − 19.54 kcal/mol.

Conclusions

The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.
LncRNA SNHG6 role in clinicopathological parameters in cancers
Authors: Khan Khushbukhat , Irfan Muhammad , Sattar Areej Abdul , Faiz Manal Bint , Rahman Anees ur , Athar Hafsa , Calina Daniela , Sharifi-Rad Javad , Cho William C.
Published: September 2023

RNA sequencing has revealed that a substantial portion of the human genome undergoes transcription, yet a minimal fraction of these transcripts translates into proteins. LncRNAs, RNA molecules less than 200 nt in length, once deemed as transcriptional noise, have now emerged as crucial regulators of numerous cellular processes. This review focuses on the lncRNA SNHG6, aiming to elucidate its biogenesis, the pivotal roles it plays, and its mechanisms in facilitating the hallmarks of cancer. A comprehensive literature review and analysis were undertaken to delve into the biogenesis of SNHG6, its roles in cellular processes, and the mechanisms through which it contributes to the hallmarks of cancer. SNHG6 is a notable lncRNA, observed to be overexpressed in various cancer types; its perturbation has been linked to tumor progression, emphasizing its significance in oncogenesis. This lncRNA contributes to a range of cellular aberrations, influencing transcriptional, post-transcriptional, and epigenetic processes of mRNA, ultimately driving cancerous transformations. LncRNA SNHG6 serves as a potential biomarker and therapeutic target due to its association with tumorigenesis. Understanding its mechanism and role in cancer can pave the way for novel diagnostic and therapeutic strategies.
Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome
Authors: Newman N. K. , Zhang Y. , Padiadpu J. , Miranda C. L. , Magana A. A. , Wong C. P. , Hioki K. A. , Pederson J. W. , Li Z. , Gurung M. , Bruce A. M. , Brown K. , Bobe G. , Sharpton T. J. , Shulzhenko N. , Maier C. S. , Stevens J. F. , Gombart A. F. , Morgun A.
Published: September 2023

Background

The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition.

Results

In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S rRNA sequences and systemic metabolic phenotypic data using a Transkingdom Network Analysis. By incorporating cell type information from single-cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reduced levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo.

Conclusions

Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. TXN primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in white adipose tissue.
Clinical validation of an AI-based automatic quantification tool for lung lobes in SPECT/CT
Authors: Verrecchia-Ramos Emilie , Morel Olivier , Ginet Merwan , Retif Paul , Ben Mahmoud Sinan
Published: September 2023

Background

Lung lobar ventilation and perfusion (V/Q) quantification is generally obtained by generating planar scintigraphy images and then imposing three equally sized regions of interest on the data of each lung. This method is fast but not as accurate as SPECT/CT imaging, which provides three-dimensional data and therefore allows more precise lobar quantification. However, the manual delineation of each lobe is time-consuming, which makes SPECT/CT incompatible with the clinical workflow for V/Q estimation. An alternative may be to use artificial intelligence-based auto-segmentation tools such as AutoLung3D (Siemens Healthineers, Knoxville, USA), which automatically delineate the lung lobes on the CT data acquired with the SPECT data. The present study assessed the clinical validity of this approach relative to planar scintigraphy and manual quantification in SPECT/CT.

Methods

The Autolung3D software was tested on the retrospective SPECT/CT data of 43 patients who underwent V/Q scintigraphy with 99mTc-macroaggregated albumin and 99mTc-labeled aerosol. It was compared to planar scintigraphy and SPECT/CT using the manual quantification method in terms of relative lobar V/Q quantification values and interobserver variability.

Results

The three methods provided similar V/Q estimates for the left lung lobes and total lungs. However, compared to the manual SPECT/CT method, planar scintigraphy yielded significantly higher estimates for the middle right lobe and significantly lower estimates for the superior and inferior right lobes. The estimates of the manual and automated SPECT/CT methods were similar. However, the post-processing time in the automated method was approximately 5 min compared to 2 h for the manual method. Moreover, the automated method associated with a drastic reduction in interobserver variability: Its maximal relative standard deviation was only 5%, compared to 23% for planar scintigraphy and 19% for the manual SPECT/CT method.

Conclusions

This study validated the AutoLung3D software for general clinical use since it rapidly provides accurate lobar quantification in V/Q scans with markedly less interobserver variability than planar scintigraphy or the manual SPECT/CT method.
Microleakage along the implant–abutment interface: a systematic review and meta-analysis of in vitro studies
Authors: Mao Zhen , Beuer Florian , Wu Daomin , Zhu Qiuyan , Yassine Jamila , Schwitalla Andreas , Schmidt Franziska
Published: September 2023

Purpose

This systematic review aimed to evaluate the incidence of microleakage events (IME) and to identify the potential factors influencing the sealing ability of the implant–abutment interface (IAI) under in vitro investigation.

Material and methods

An electronic search of MEDLINE (PubMed), EMBASE, and Web of Science databases, combined with a manual literature search was conducted up to September 2022. In vitro studies that reported the degree of microleakage at IAI under dynamic loading conditions were included. A meta-analysis was performed to calculate the mean values of the incidence of microleakage events. Subgroup analysis and meta-regression were conducted to further investigate the effect of different variables.

Results

675 studies were identified following the search process and 17 in vitro studies were selected according to the eligibility criteria. The weighted mean incidence of microleakage events was 47% (95% confidence interval: [0.33, 0.60]), indicating that contamination was observed in nearly half of the samples. Concerning possible factors that may influence microleakage (e.g., loading condition, assessment method, implant–abutment connection design, types of abutment material, the use of sealing agents), loading condition (p = 0.016) was the only variable that significantly influenced IME in the meta-regression analysis.

Conclusions

The results demonstrated that dynamic loading significantly increases the potential of bacterial penetration at the implant–abutment junction. The results should be interpreted carefully due to the data heterogeneity and further well-conducted in vitro studies with homogeneous samples are needed to standardize the methodologies.

Graphical Abstract
Does financial development moderate the link between technological innovation and environmental indicators? An advanced panel analysis
Authors: Fakher Hossein Ali , Ahmed Zahoor
Published: September 2023

This study analyzes the role of financial development (FD) on the impact of technological innovation (TI) on six environmental quality indicators for the 25 economies that are part of the Organization for Economic Cooperation and Development for the period from 2000 to 2019. We use a two-step dynamic generalized method of moments approach to understand this relationship. The results show that FD augments the positive effects of TI on four of the six environmental indicators, namely ecological footprint, adjusted net savings, pressure on nature, and environmental performance. However, no significant effects on environmental sustainability and environmental vulnerability indices were found. When considering all of the environmental quality indicators, TI appears to enhance environmental quality. We find evidence to support the existence of the environmental Kuznets curve in the context of each environmental indicator and economic growth. Moreover, FD and energy consumption appear to accelerate environmental degradation. Based on these results, FD should be viewed as an important parameter in designing policies for innovation to achieve the goal of net-zero carbon emissions.
Study of insight in patients with obsessive compulsive disorder and its relation to executive functions and serum brain-derived neurotrophic factor
Authors: Soltan Mohamed R. , Dessoki Hani H. , Abbas Mohammed M. , Mahmoud Lamiaa H. , Dawoud Mariam E.
Published: September 2023

Background

Obsessive–compulsive disorder (OCD) is usually associated with insight’s heterogeneity, and those with poor insight showed lower BDNF and cognitive deficiencies. The aim was to detect the relation between insight to executive dysfunction and BDNF.

Materials and methods

Forty patients diagnosed with OCD and forty matched healthy controls. Also, both poor and good insight groups (assessed by The Brown Assessment of Belief Scale) were compared as regard Trail Making Test and serum level of BDNF).

Results

OCD patients group gave a significant worse performance in TMT and lower BDNF serum level than healthy control. Also, OCD patients with poor insight had lower BDNF level than patients with good to fair insight. ROC curve analysis confirmed that BDNF is a valuable diagnostic biomarker of insight in patients with OCD with 100% sensitivity and 72.41% specificity, p value < 0.001. Insight of OCD patients was not significantly associated with executive dysfunction detected by Trail Making Test.

Conclusions

OCD patients with poor insight had longer duration of illness, severe OCD symptoms, lower serum BDNF level, and longer time on TMTA-B than good insight patients. BDNF is a valuable diagnostic biomarker of insight in patients with OCD.
Postoperative atrial fibrillation after thoracic surgery (PoAF): risk factors and outcome
Authors: Scheggi Valentina , Menale Silvia , Marcucci Rossella , Dematté Anna , Giovacchini Jacopo , Cenni Noemi , Vitale Giorgio , Alterini Bruno , Salvicchi Alberto , Tamburini Matteo , Musmeci Salvatore , Bongiolatti Stefano , Voltolini Luca , Marchionni Niccolò
Published: September 2023

Background

Postoperative AF (PoAF) is a common complication of the early postoperative period of noncardiac, thoracic surgery and is associated with prolonged hospital stay. In order to investigate the predictors of PoAF in the specific setting of lung surgery of oncologic patients, we retrospectively analyzed 338 consecutive patients admitted to our department to be operated for lung cancer with a thoracotomy approach (i.e., open surgery). We determined this population’s prevalence, risk factors, and consequences of PoAF.

Results

PoAF occurred in 35/338 (10.4%) patients and was significantly more frequent in older patients, with a best predictive value of 71 years at ROC curve analysis (AUC 0.70, p < 0.001) and in those with chronic renal failure (p = 0.01). The left atrial area was also significantly associated with the risk of PoAF (AUC 0.78, p = 0.000). PoAF was more frequent in patients with small cell and squamous cell carcinoma (p = 0.03). The occurrence of PoAF was associated with a longer hospital stay (p = 0.001) but not with higher long-term mortality (follow-up mean length: 3.3 ± 0.3 years). At multivariable analysis, the only independent predictors of PoAF were age (OR for 1-year increase 1.089, 95% CI 1.039–1.141, p 0.001) and open surgery (OR 2.07, 95% CI 1.0–4.29, p 0.047). At the 3-year follow-up, all patients were in sinus rhythm.

Conclusions

The present study shows the association between age and open surgery with PoAF, furtherly highlighting that the incidence of arrhythmia leads to a longer hospital stay. Left atrium dilatation could identify at-risk patients. Those results suggest that older patients — especially those with larger left atrium areas — might benefit most from a VATS approach to further reduce the arrhythmia incidence. Such a finding supports the indication of a systematic echocardiographic evaluation before elective lung surgery, especially in patients with known clinical risk factors.
The effect of slope height and angle on the safety factor and modes of failure of 3D slopes analysis using limit equilibrium method
Authors: Kumar Sumit , Choudhary Shiva Shankar , Burman Avijit
Published: September 2023

Background

It is a well-known fact that the safety of slopes majorly depends on several factors such as geometry, soil properties. The safety factor might change significantly depending on the soil type and the slope’s shape. The knowledge of the nature of the change in the safety factor due to the change in the slope’s height and angle is essential for implementing an effective strategy of increasing the safety factor for any slope stability problem. The influence of geometric shapes on the stability of the slope needs to be properly investigated through three-dimensional slope stability analysis, as the three-dimensional analysis is suitable for all slopes, even those which invalidate the plane-strain conditions.

Results

To calculate the three-dimensional safety factor, multiple analyses of three homogenous soil slopes with different soil properties were conducted by varying slope height, angle, and combinations. Each slope's height and angle were recorded to identify the types of slope failure. The analysis’s findings showed that while a decrease in height raises the safety factor nonlinearly, a decrease in slope angle increases the safety factor almost linearly. Base failure is the most likely failure for slopes with a height less than 4.0 m and an angle of inclination less than 18°. On clay and sandy clay soils, toe slide is the most common type of slope failure. The expected failure type will be either toe or face failure when the slope's height and base angle exceeds 5.0 m and 22°, respectively. This study also found that the three-dimensional safety factor for soil slope is generally 10–20% higher than the two-dimensional factor of slope safety.

Conclusions

The slope’s nature depended on the soil type and slope form, but the safety factor increased as the slope angle and height decreased. To determine the most efficient method for slope stabilization, it is necessary to do an extensive study on slope height and angle reduction techniques. It should be ensured that the sliding mass of soil does not rise, resulting in a potential slope failure. The present study will help identify the correlation between the height and base inclination of the slope with the expected nature of slope failure. The present study helps to investigate the variation of the safety factor of a three-dimensional homogenous soil slope subjected to self-weight only. The study can be further extended to observe the variation of the factor of safety for a 3D slope subjected to pore water pressure and seismic loading also.
Unilateral vocal cord palsy during COVID-19 era: a study from a tertiary care centre in India
Authors: Sahai Anoushka , Marfatia Hetal , Gaikwad Ashwinikumar , Agarwal Anushka , Narkhede Kartik , Jadhav Mruganayani , Katkar Sanket
Published: September 2023

Background

In otolaryngology outpatient clinics, patients frequently present with unilateral vocal cord paralysis (UVCP). During the pandemic, various new protocols were designed to identify UVCP. An experienced otolaryngologist must conduct a thorough history-taking, examination, and investigation to determine the cause of UVCP.

Objectives

To evaluate various causes of UVCP during the pandemic.

Methods

Thirty patients with UVCP on 70-degree rigid endoscopy were studied. Detailed general and systemic examinations were done. All COVID-19 precautions were followed during the evaluation, and real-time reverse transcription-polymerase chain reaction was done before the endoscopic procedure. High-resolution computed tomography scan of skull base to mediastinum with contrast was performed for etiology. Patients were treated according to the standard protocols. Follow-up at 1, 3, and at 6 months was performed.

Results

The mean age was 42.3 ± 14.83 years. All the patients had presented with a change in voice. Twenty percent had UVCP post a surgical procedure. No cause could be found in 16.67% of patients. Five patients had succumbed to complications relating to their other prevailing conditions. At 6 months, 10 patients continued to have palsy, 9 showed paresis, and 6 showed complete mobility of the cords.

Conclusion

During the pandemic, diagnosing and following up such patients were a challenge. Investigating a cause of UVCP, the symptoms of which might be trivial at presentation, leads to discover a much sinister cause. UVCP in post-covid mucormycosis was an entity requiring multimodality management. Pandemic-induced restrictions lead to formulations of newer protocols for tackling this entity.