bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of macromolecular phenotype of human skeletal muscle in diabetes using infrared spectroscopy
Authors: Zupančič Barbara , Ugwoke Chiedozie Kenneth , Abdelmonaem Mohamed Elwy Abdelhamed , Alibegović Armin , Cvetko Erika , Grdadolnik Jože , Šerbec Anja , Umek Nejc
Published: December 2023

Introduction

The global burden of diabetes mellitus is escalating, and more efficient investigative strategies are needed for a deeper understanding of underlying pathophysiological mechanisms. The crucial role of skeletal muscle in carbohydrate and lipid metabolism makes it one of the most susceptible tissues to diabetes-related metabolic disorders. In tissue studies, conventional histochemical methods have several technical limitations and have been shown to inadequately characterise the biomolecular phenotype of skeletal muscle to provide a holistic view of the pathologically altered proportions of macromolecular constituents.

Materials and methods

In this pilot study, we examined the composition of five different human skeletal muscles from male donors diagnosed with type 2 diabetes and non-diabetic controls. We analysed the lipid, glycogen, and collagen content in the muscles in a traditional manner with histochemical assays using different staining techniques. This served as a reference for comparison with the unconventional analysis of tissue composition using Fourier-transform infrared spectroscopy as an alternative methodological approach.

Results

A thorough chemometric post-processing of the infrared spectra using a multi-stage spectral decomposition allowed the simultaneous identification of various compositional details from a vibrational spectrum measured in a single experiment. We obtained multifaceted information about the proportions of the different macromolecular constituents of skeletal muscle, which even allowed us to distinguish protein constituents with different structural properties. The most important methodological steps for a comprehensive insight into muscle composition have thus been set and parameters identified that can be used for the comparison between healthy and diabetic muscles.

Conclusion

We have established a methodological framework based on vibrational spectroscopy for the detailed macromolecular analysis of human skeletal muscle that can effectively complement or may even serve as an alternative to histochemical assays. As this is a pilot study with relatively small sample sets, we remain cautious at this stage in drawing definitive conclusions about diabetes-related changes in skeletal muscle composition. However, the main focus and contribution of our work has been to provide an alternative, simple and efficient approach for this purpose. We are confident that we have achieved this goal and have brought our methodology to a level from which it can be successfully transferred to a large-scale study that allows the effects of diabetes on skeletal muscle composition and the interrelationships between the macromolecular tissue alterations due to diabetes to be investigated.
The mitigation effectiveness of farmers’ adaptation measures for seasonal drought: evidence from major rice growing areas in southern China
Authors: Zhu Kangrui , Xu Wen , Chen Boou
Published: December 2023

To assess the mitigation effectiveness of farmers’ adaptation measures for seasonal drought, we focused on the 2013 seasonal drought disaster in Jiangxi Province, southern China, the major rice growing areas, a typical case from China. First, we surveyed 755 farm households in Jiangxi Province that were harmed by seasonal drought in 2013. Based on the data from this survey, we constructed econometric models and used an instrumental variable approach to evaluate the effects of adaptation measures on the rice yield reduction due to seasonal drought, and then examined the factors influencing the capacity of farmers to adopt effective adaptation measures. The results show that: 1) More adaptation measures adopted by farmers can be effective in reducing the negative impacts of seasonal droughts on rice production. 2) All three types of measures, structural adjustment adaptation measures (SAAM), irrigation adaptation measures (IAM) and engineering adaptation measures (EAM) can significantly mitigate rice yield reduction due to seasonal drought, and SAAM and IAM perform more effectively. 3) Farmers’ social communication, frequency of droughts and access to disaster prevention information can help to increase the capacity of farmers to adopt adaptation measures, while distance from roads has a negative effect. 4) In terms of the different supportive policies, policies with higher-level agents and human support are more effective in increasing the ability of farmers to adopt adaptation measures. Our findings provide the following policy insights. On the one hand, it is necessary to increase the capacity of farmers to adopt measures by improving their social communication, incentivizing them to access information on resilience, and providing more supportive policies, especially policies with higher-level agents and human support. On the other hand, farmers should be encouraged to actively adopt adaptation measures to reduce the hazards of seasonal drought, especially SAAM and IAM.
High-resolution sea-level fluctuations during the Mid-Holocene in the Ningshao Coastal Plain region, eastern China
Authors: Ling Chaohao , Xue Bin , Yao Shuchun , Zhang Wenchao , Pan Dadong , Tang Lingyu
Published: December 2023

Sea level changes during the Mid-Holocene directly influenced the Neolithic culture in the Yangtze River Delta region (YRD). However, the high-resolution sea level change characteristics for this period remain unclear. In this study, we performed a high-resolution palynological analysis, including pollen, Dinoflagellate cysts, and Foraminiferal organic linings, using a high-resolution sediment core from Shanglin Lake, in the North of Ningshao Plain (the south of Hangzhou Bay). 11 accelerator mass spectrometry 14C(AMS) datings indicate the age of the sediments range from 8 cal ka B.P. to 5.6 cal ka B.P. The results show that during the Mid-Holocene, Shanglin Lake evolved from an estuary – subtidal lagoon – semi-enclosed bay – semi-enclosed lagoon – semi-enclosed bay – enclosed lagoon to a modern freshwater lake. There was a period of no, or minimal, eustatic sea-level rise between 7733 and 7585 cal yr B.P. The Mid-Holocene high sea level comes in 7253–7082 cal yr BP. Between 7000 cal yr BP and 5502 cal yr BP, the sea level is close to modern value. The sea level change during this period had a significant impact on the local Neolithic human activity.
Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth
Authors: Onyango Stanley , Mi Jia Dai , Koech Angela , Okiro Patricia , Temmerman Marleen , von Dadelszen Peter , Tribe Rachel M. , Omuse Geoffrey ,   the PRECISE Network
Published: December 2023

Differences in the cervicovaginal microbiota are associated with spontaneous preterm birth (sPTB), a significant cause of infant morbidity and mortality. Although establishing a direct causal link between cervicovaginal microbiota and sPTB remains challenging, recent advancements in sequencing technologies have facilitated the identification of microbial markers potentially linked to sPTB. Despite variations in findings, a recurring observation suggests that sPTB is associated with a more diverse and less stable vaginal microbiota across pregnancy trimesters. It is hypothesized that sPTB risk is likely to be modified via an intricate host-microbe interactions rather than due to the presence of a single microbial taxon or broad community state. Nonetheless, lactobacilli dominance is generally associated with term outcomes and contributes to a healthy vaginal environment through the production of lactic acid/maintenance of a low pH that excludes other pathogenic microorganisms. Additionally, the innate immunity of the host and metabolic interactions between cervicovaginal microbiota, such as the production of bacteriocins and the use of proteolytic enzymes, exerts a profound influence on microbial populations, activities, and host immune responses. These interplays collectively impact pregnancy outcomes. This review aims to summarize the complexity of cervicovaginal environment and microbiota dynamics, and associations with bacterial vaginosis and sPTB. There is also consideration on how probiotics may mitigate the risk of sPTB and bacterial vaginosis.
Hysteroscopic hysteroplasty for the treatment of T-shaped uteri in women with reproductive failure
Authors: Ying Lu , Li Zhang , Shangping Du , Tong Zhou , Liguo Li , Qiaoli Tong
Published: December 2023

Objective

To evaluate the efficacy of hysteroscopic hysteroplasty in the treatment of uterine malformation complicated by primary reproductive disorders.

Methods

Women with unexplained primary infertility, repeated in vitro fertilization (IVF) failure or repeated spontaneous abortion, and uterine malformations unrelated to diethylstilbestrol who visited the obstetrics and gynecology department of our hospital from January 2019 to December 2022 were included in the prospective cohort study. Uterine malformation in the patients was confirmed by three-dimensional ultrasound and diagnostic hysteroscopy. Hysteroscopic hysteroplasty was performed using a 5-mm diameter hysteroscope and 5-FR surgical scissors, and after 3 months, palliative care was proposed for patients with unexplained infertility or repeated spontaneous abortion, and after 6 months, IVF treatment was recommended for patients with repeated in vitro fertilization (IVF) failures, with a planned minimum follow-up time of 1 year.

Results

A total of 83 women enrolled in the study, including 33 cases of primary infertility, 29 cases of repeated spontaneous abortion, and 21 cases of repeated IVF failure. No complications occurred during the hysteroscopic surgery. During the follow-up period, the clinical pregnancy rate of the women enrolled in the study increased to 77.1%, the live birth rate went up to 79.7%, the fetus delivered at full term accounted for 64.1%, and the cesarean section rate was 27.5%. The miscarriage rate was 9.4%.

Conclusion

Hysteroscopic hysteroplasty can improve the reproductive outcomes in women with primary reproductive disorders and uterine malformations.
A founder COL4A3 pathogenic variant resulting in Alport syndrome and thin basement membrane disease: a case report series
Authors: Tkemaladze Tinatin , Bregvadze Kakha , Kvaratskhelia Eka , Abzianidze Elene , Davitaia Tinatin
Published: December 2023

Alport syndrome is a rare genetic condition characterized by kidney disease, hearing impairment, and ocular abnormalities. It exhibits various inheritance patterns involving pathogenic variants in COL4A3, COL4A4, and COL4A5 genes. The phenotypes can range from isolated hematuria with a non-progressive or very slowly progressive course to progressive kidney disease with extrarenal abnormalities. Timely diagnosis of Alport syndrome facilitates the early and effective implementation of treatment, as well as genetic counseling. Here, we report the COL4A3 c.765G > A, p.((=)) mutation in three ethnically Azerbaijani, apparently unrelated, consanguineous families from the village of Algeti in the Marneuli region of Georgia. We speculate that this variant could represent a founder mutation within this population and recommend offering genetic testing to Algeti village residents with persistent hematuria.
Association of Life's Essential 8 with osteoarthritis in United States adults: mediating effects of dietary intake of live microbes
Authors: Gou Ruoyu , Chang Xiaoyu , Li Zeyuan , Pan Ying , Li Guanghua
Published: December 2023

Objective

Osteoarthritis (OA) is associated with cardiovascular disease and represents a persistent economic and physical burden on patients in the United States. This study evaluated the mediating effect of dietary live microbe intake on the association between cardiovascular health [based on Life's Essential 8 (LE8) scores] and osteoarthritis (OA) in adults.

Methods

This cross-sectional study included data from the National Health and Nutrition Examination Survey, 1999–2019 (from patients aged ≥20 years). LE8 scores (0–100) were measured according to the American Heart Association definition and categorized as low (0–49), moderate (50–79), or high (80–100). OA disease status was assessed using self-reported data from patients. The relationships were evaluated using multivariate logistic and restricted cubic spline models. Mediation analysis was used to evaluate the mediating effect of dietary live microbe intake on the association between LE8 and OA risk.

Results

The study included 23,213 participants aged ≥20 years. After adjusting for latent confounders, higher LE8 scores were found to be associated with a lower incidence of OA. The odds ratios (with 95% confidence intervals) for low, moderate, and high OA risk were 0.81 (0.69, 0.96) and 0.55 (0.44, 0.69), respectively; a non-linear dose-response relationship was observed (P-nonlinear = 0.012). Health behavior and health factor scores showed a similar pattern of correlation with OA risk. Low live microbe intake mediated the association between LE8, health behavior, and health factor scores with OA risk and did not appear to reduce OA risk.

Conclusion

Our findings suggest that although higher LE8 scores reduce the risk of developing OA, low live microbe intake may reduce the protective effect of higher scores. It is, therefore, essential to emphasize adherence to a lifestyle that confers high LE8 scores. Individuals should also be advised to reduce the intake of foods with low live microbe content.
Conservation and diversity of the pollen microbiome of Pan-American maize using PacBio and MiSeq
Authors: Khalaf Eman M. , Shrestha Anuja , Reid Michelle , McFadyen Benjamin J. , Raizada Manish N.
Published: December 2023

Pollen is a vector for diversification, fitness-selection, and transmission of plant genetic material. The extent to which the pollen microbiome may contribute to host diversification is largely unknown, because pollen microbiome diversity within a plant species has not been reported, and studies have been limited to conventional short-read 16S rRNA gene sequencing (e.g., V4-MiSeq) which suffers from poor taxonomic resolution. Here we report the pollen microbiomes of 16 primitive and traditional accessions of maize (corn) selected by indigenous peoples across the Americas, along with the modern U.S. inbred B73. The maize pollen microbiome has not previously been reported. The pollen microbiomes were identified using full-length (FL) 16S rRNA gene PacBio SMRT sequencing compared to V4-MiSeq. The Pan-American maize pollen microbiome encompasses 765 taxa spanning 39 genera and 46 species, including known plant growth promoters, insect-obligates, plant pathogens, nitrogen-fixers and biocontrol agents. Eleven genera and 13 species composed the core microbiome. Of 765 taxa, 63% belonged to only four genera: 28% were Pantoea, 15% were Lactococcus, 11% were Pseudomonas, and 10% were Erwinia. Interestingly, of the 215 Pantoea taxa, 180 belonged to a single species, P. ananatis. Surprisingly, the diversity within P. ananatis ranged nearly 10-fold amongst the maize accessions analyzed (those with ≥3 replicates), despite being grown in a common field. The highest diversity within P. ananatis occurred in accessions that originated near the center of diversity of domesticated maize, with reduced diversity associated with the north–south migration of maize. This sub-species diversity was revealed by FL-PacBio but missed by V4-MiSeq. V4-MiSeq also mis-identified some dominant genera captured by FL-PacBio. The study, though limited to a single season and common field, provides initial evidence that pollen microbiomes reflect evolutionary and migratory relationships of their host plants.
Maxizyme-mediated suppression of chikungunya virus replication and transmission in transgenic Aedes aegypti mosquitoes
Authors: Mishra Priya , Balaraman Velmurugan , Fraser Malcolm J.
Published: December 2023

Chikungunya virus (CHIKV) is an emerging mosquito-borne pathogen of significant public health importance. There are currently no prophylactic vaccines or therapeutics available to control CHIKV. One approach to arbovirus control that has been proposed is the replacement of transmission-competent mosquitoes with those that are refractory to virus infection. Several transgene effectors are being examined as potentially useful for this population replacement approach. We previously demonstrated the successful use of hammerhead ribozymes (hRzs) as an antiviral effector transgene to control CHIKV infection of, and transmission by, Aedes mosquitoes. In this report we examine a maxizyme approach to enhance the catalytic activity and prevent virus mutants from escaping these ribozymes. We designed a maxizyme containing minimized (monomer) versions of two hRzs we previously demonstrated to be the most effective in CHIKV suppression. Three versions of CHIKV maxizyme were designed: Active (Mz), inactive (ΔMz), and a connected CHIKV maxizyme (cMz). The maxizymes with their expression units (Ae-tRNA val promoter and its termination signal) were incorporated into lentivirus vectors with selection and visualization markers. Following transformation, selection, and single-cell sorting of Vero cells, clonal cell populations were infected with CHIKV at 0.05 and 0.5 MOI, and virus suppression was assessed using TCID50-IFA, RT-qPCR, and caspase-3 assays. Five transgenic mosquito lines expressing cMz were generated and transgene insertion sites were confirmed by splinkerette PCR. Our results demonstrate that Vero cell clones expressing Mz exhibited complete inhibition of CHIKV replication compared to their respective inactive control version or the two parent hRzs. Upon oral challenge of transgenic mosquitoes with CHIKV, three out of the five lines were completely refractory to CHIKV infection, and all five lines tested negative for salivary transmission. Altogether, this study demonstrates that maxizymes can provide a higher catalytic activity and viral suppression than hRzs.
Custom order entry for Parkinson’s medications in the hospital improves timely administration: an analysis of over 31,000 medication doses
Authors: Azmi Hooman , Cocoziello Lisa , Ruzicka Francis , Clar Elana , Pederson John Michael , Jacob Blessy , Thomas Jewell , Rocco Anthony , Bobek Mary , Pereira-Argenziano Lucy , Roth Patrick , Thomas Florian P.
Published: December 2023

Background

Patients with Parkinson’s disease (PD) are at increased risk for hospital acquired complications. Deviations from home medication schedules and delays in administration are major contributing factors. We had previously developed a protocol to ensure adherence to home medication schedules using “custom” ordering. In this study we are assessing the impact this order type may have on reducing delays in PD medication administration in the hospital.

Material and methods

We reviewed 31,404 orders placed for PD medications from January 2, 2016 to April 30 2021. We evaluated the orders to determine if they were placed in a Custom format or using a default non-custom order entry. We further evaluated all orders to determine if there was a relationship with the order type and timely administration of medications. We compared medications that were administered within 1 min, 15 min, 30 min and 60 min of due times across custom orders vs. non-custom default orders. We also evaluated the relationship between ordering providers and type of orders placed as well as hospital unit and type of orders placed.

Results

14,204 (45.23%) orders were placed using a custom schedule and 17,200 (54.77%) orders were placed using non-custom defaults. The custom group showed a significantly lower median delay of 3.06 minutes compared to the non-custom group (p<.001). Custom orders had a significantly more recent median date than non-custom default orders (2019-10-07 vs. 2018-01-06, p<0.001). In additional analyses, medication administration delays were significantly improved for custom orders compared to non-custom orders, with likelihoods 1.64 times higher within 1 minute, 1.40 times higher within 15 minutes, and 1.33 times higher within 30 minutes of the due time (p<0.001 for all comparisons).

Conclusion

This is the largest study to date examining the effects of order entry type on timely administration of PD medications in the hospital. Orders placed using a custom schedule may help reduce delays in administration of PD medications.
Predicting the need for cerebrospinal fluid shunt implantation after spontaneous intracerebral hemorrhage: a challenging task
Authors: Khalaveh Farjad , Zeiser Vitalij , Cho Anna , Schmelzer Sophie , Reinprecht Andrea , Herta Johannes , Roessler Karl , Dorfer Christian
Published: December 2023

Objectives

The development of persistent hydrocephalus in patients after spontaneous intracerebral hemorrhage (ICH) is still poorly understood, and many variables predicting the need for a cerebrospinal fluid (CSF)-shunt have been described in the literature with varying results. The aim of this study is to find predictive factors for shunt dependency.

Methods

We performed a retrospective, single-center study of 99 neurosurgically treated patients with spontaneous ICH. Variables, including age, Glasgow Coma Scale (GCS), intraventricular hemorrhage (IVH), location of hemorrhage, acute hydrocephalus, and volumetric analysis of IVH, ICH, and intraventricular CSF were compared between patients with and without CSF-shunt implantation. Furthermore, receiver operating characteristics (ROC) for ICH, IVH, and intraventricular CSF volume parameters were calculated.

Results

CSF-shunt implantation was performed significantly more often in patients after thalamic (p = 0.03) and cerebellar ICH (p = 0.04). Moreover, a lower ratio between the total hemorrhage volume and intraventricular CSF volume (p = 0.007), a higher IVH distribution in the third ventricle, and an acute hydrocephalus (p < 0.001) with an increased intraventricular CSF volume (p < 0.001) were associated with shunt dependency. Our ROC model demonstrated a sensitivity of 82% and a specificity of 65% to predict the necessity for a shunt at a cutoff value of 1.9 with an AUC of 0.835.

Conclusion

Volumetric analysis of ICH, IVH, and intraventricular CSF may improve the prediction of CSF shunt implantation in patients with spontaneous ICH.
TSP-GNN: a novel neuropsychiatric disorder classification framework based on task-specific prior knowledge and graph neural network
Authors: Lang Jinwei , Yang Li-Zhuang , Li Hai
Published: December 2023

Neuropsychiatric disorder (ND) is often accompanied by abnormal functional connectivity (FC) patterns in specific task contexts. The distinctive task-specific FC patterns can provide valuable features for ND classification models using deep learning. However, most previous studies rely solely on the whole-brain FC matrix without considering the prior knowledge of task-specific FC patterns. Insight by the decoding studies on brain-behavior relationship, we develop TSP-GNN, which extracts task-specific prior (TSP) connectome patterns and employs graph neural network (GNN) for disease classification. TSP-GNN was validated using publicly available datasets. Our results demonstrate that different ND types show distinct task-specific connectivity patterns. Compared with the whole-brain node characteristics, utilizing task-specific nodes enhances the accuracy of ND classification. TSP-GNN comprises the first attempt to incorporate prior task-specific connectome patterns and the power of deep learning. This study elucidates the association between brain dysfunction and specific cognitive processes, offering valuable insights into the cognitive mechanism of neuropsychiatric disease.
Alterations in cognitive function and blood biomarkers following transcranial direct current stimulation in patients with amyloid positron emission tomography-positive Alzheimer’s disease: a preliminary study
Authors: Kim Jinuk , Yang YoungSoon
Published: December 2023

Introduction

Alzheimer’s disease (AD), the most common form of dementia, is characterized by progressive cognitive decline. To address this, we conducted a randomized, double-blinded, sham-controlled study to investigate the therapeutic potential of transcranial direct current stimulation (tDCS) on patients with amyloid positron emission tomography (PET)- positive AD.

Methods

Participants already undergoing pharmacological treatment and testing positive for amyloid PET were divided into Active-tDCS (n = 8) and Sham-tDCS (n = 8) groups. For 12 weeks, participants or their caregivers administered daily bi-frontal tDCS (YMS-201B+, Ybrain Inc., Seongnam, Korea) at home (2 mA, 30 min). Pre- and post-intervention assessments included neuropsychological tests and blood sample measurements for oligomerized beta-amyloid.

Results

The Active-tDCS group demonstrated significant improvements in cognitive domains such as language abilities, verbal memory, and attention span and in frontal lobe functions compared to the Sham-tDCS group. Furthermore, the Active-tDCS group showed a marked reduction in post-intervention plasma Aβ oligomerization tendency level, suggesting changes in pivotal AD-associated biomarkers.

Discussion

Our results emphasize the potential therapeutic benefits of tDCS for mild AD patients with amyloid PET positivity and stress the urgency for broader research, considering the global challenges of dementia and the need to pursue innovative therapeutic strategies.
Differential contribution of TrkB and p75NTR to BDNF-dependent self-renewal, proliferation, and differentiation of adult neural stem cells
Authors: Lozano-Ureña Anna , Frade José M.
Published: December 2023

Alterations in adult neurogenesis are a common hallmark of neurodegenerative diseases. Therefore, understanding the molecular mechanisms that control this process is an indispensable requirement for designing therapeutic interventions addressing neurodegeneration. Neurotrophins have been implicated in multiple functions including proliferation, survival, and differentiation of the neural stem cells (NSCs), thereby being good candidates for therapeutic intervention. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family and has been proven to promote neurogenesis in the subgranular zone. However, the effects of BDNF in the adult subventricular zone (SVZ) still remain unclear due to contradictory results. Using in vitro cultures of adult NSCs isolated from the mouse SVZ, we show that low concentrations of BDNF are able to promote self-renewal and proliferation in these cells by activating the tropomyosin-related kinase B (TrkB) receptor. However, higher concentrations of BDNF that can bind the p75 neurotrophin receptor (p75NTR) potentiate TrkB-dependent self-renewal and proliferation and promote differentiation of the adult NSCs, suggesting different molecular mechanisms in BDNF-promoting proliferation and differentiation. The use of an antagonist for p75NTR reduces the increment in NSC proliferation and commitment to the oligodendrocyte lineage. Our data support a fundamental role for both receptors, TrkB and p75NTR, in the regulation of NSC behavior.
Chemical and biochemical characterization of Ipomoea aquatica: genoprotective potential and inhibitory mechanism of its phytochemicals against α-amylase and α-glucosidase
Authors: Saikia Kangkon , Dey Saurav , Hazarika Shabiha Nudrat , Handique Gautam Kumar , Thakur Debajit , Handique Arun Kumar
Published: December 2023

Ipomea aquatica, also known as water spinach, is an aquatic non-conventional leafy vegetable and is considered a healthy and seasonal delicacy in ethnic food culture. The study revealed the presence of rich chemical and biochemical composition in I. aquatica and antioxidant activities. Moreover, the plant extracts demonstrated significant DNA damage prevention activity against UV/H2O2-induced oxidative damage. High-resolution mass spectrometric analysis by UPLC-qTOF-MS/MS resulted in the identification of over 65 different compounds and 36 important secondary metabolites. Most of the compounds identified represented polyphenolic compounds, viz. polyphenol glycosides and phenolic acids, followed by alkaloids and terpenoids. A UPLC-DAD method was developed and quantified for 10 different polyphenolic compounds. Out of all the metabolites examined, a significant number of compounds were reported to have various bioactive properties, including antibacterial, antiviral, antitumor, hepatoprotection, and anti-depressant effects. The plant extracts were found to contain various compounds, including euphornin, lucidenic acid, and myricitin glycosides, which possess significant medicinal value. Metabolite analysis utilizing GC–MS revealed the presence of various fatty acids, amino acids, sugars, and organic acids. The analysis revealed the presence of essential unsaturated fatty acids such as α-linolenic acid as well as beneficial substances such as squalene., The evaluation of glycemic control activity was carried out by comprehending the inhibitory potential of α-amylase and α-glucosidase, outlining the kinetics of the inhibition process. The inhibitory activities were compared to those of acarbose and revealed stronger inhibition of α-glucosidase as compared to α-amylase. Furthermore, the mechanism of inhibition was determined using in silico analysis, which involved molecular docking and molecular dynamic simulation of the identified IA phytochemicals complexed with the hydrolase enzymes. The study generates convincing evidence that dietary intake of I. aquatica provides a positive influence on glycemic control along with various health-protective and health-promoting benefits.
Clinical value of conventional magnetic resonance imaging combined with diffusion-weighted imaging in predicting pelvic lymph node metastasis of cervical cancer
Authors: Fan Leilei , Ma Liguo , Ling Rennan , Guo Xiaojing , Li Haili , Yang Degui , Lian Zhesi
Published: December 2023

Background

In cervical cancer (CC), the involvement of pelvis lymph nodes is a crucial factor for patients’ outcome. We aimed to investigate the value of conventional magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) in predicting CC pelvic lymph node metastasis (PLNM).

Methods

This retrospective study included CC patients who received surgical treatments. Surgical pathology results served as the gold standard for investigating the diagnostic performance of conventional MRI combined with DWI. We analyzed the association between tumor ADC and PLNM, as well as other pathological factors. The areas under the receiver operating characteristic curves (AUCs) for ADC in assessing PLNM and pathological factors were evaluated, and optimal cut-off points were obtained.

Results

A total of 261 CC patients were analyzed. PLNM patients had significantly lower tumor ADC (0.829 ± 0.144×10-3mm2/s vs. 1.064 ± 0.345×10-3mm2/s, p<0.0001), than non-PLNM CC. The agreement between conventional MRI combined with DWI and pathological results on PLNM diagnosis was substantial (Kappa=0.7031, p<0.0001), with 76% sensitivity, 94.31% specificity, and 90.8% accuracy. The AUC of tumor ADC was 0.703, and the optimal cut-off was 0.95×10-3 mm2/s. In multivariate analysis model 1, tumor ADC<0.95×10-3mm2/s was significantly associated with PLNM (OR, 2.83; 95%CI, 1.08–7.43; p= 0.0346) after adjusting for age and pathological risk factors. In multivariate analysis model 2, tumor ADC<0.95×10-3mm2/s (OR, 4.00; 95%CI, 1.61–9.89; p=0.0027), age<35 years old (OR, 2.93; 95%CI, 1.04–8.30; p=0.0428), increased tumor diameter on MRI (OR, 2.17; 95%CI, 1.18–3.99; p=0.0128), vaginal vault involvement on MRI (OR, 2; 95%CI, 1.002–3.99; p=0.0494) were independent predictors for PLNM. Tumor ADC<0.95×10-3mm2/s was significantly associated with higher risk of tumor diameter ≥4cm (OR, 2.60; 95%CI, 1.43–4.73; p=0.0017), muscular layer infiltration >1/2 (OR, 5.46; 95%CI, 3.19–9.34; p<0.0001), vaginal vault involvement (OR, 2.25; 95%CI, 1.28–3.96; p=0.0051), and lymphovascular space involvement (OR, 3.81; 95%CI, 2.19–6.63; p<0.0001).

Conclusion

Conventional MRI combined with DWI had a good diagnostic performance in detecting PLNM. The tumor ADC value in PLNM patients was significantly lower than that in non-PLNM patients. Tumor ADC <0.95×10-3mm2/s, age <35 years old, increased tumor diameter on MRI, vaginal vault involvement on MRI were independent predictors for PLNM.
Desmoglein-2 as a cancer modulator: friend or foe?
Authors: Myo Min Kay K. , Ffrench Charlie B. , McClure Barbara J. , Ortiz Michael , Dorward Emma L. , Samuel Michael S. , Ebert Lisa M. , Mahoney Mỹ G. , Bonder Claudine S.
Published: December 2023

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer.
A preliminary study evaluating self-reported effects of cannabis and cannabinoids on neuropathic pain and pain medication use in people with spinal cord injury
Authors: Kinnunen Kristiina , Robayo Linda E. , Cherup Nicholas P. , Frank Scott I. , Widerström-Noga Eva
Published: December 2023

Approximately 60% of individuals with a spinal cord injury (SCI) experience neuropathic pain, which often persists despite the use of various pharmacological treatments. Increasingly, the potential analgesic effects of cannabis and cannabinoid products have been studied; however, little research has been conducted among those with SCI-related neuropathic pain. Therefore, the primary objective of the study was to investigate the perceived effects of cannabis and cannabinoid use on neuropathic pain among those who were currently or had previously used these approaches. Additionally, the study aimed to determine if common pain medications are being substituted by cannabis and cannabinoids. Participants (N = 342) were recruited from existing opt-in listserv sources within the United States. Of those, 227 met the inclusion criteria and were enrolled in the study. The participants took part in an anonymous online survey regarding past and current use of cannabis and their perceived effects on neuropathic pain, including the use of pain medication. Those in the sample reported average neuropathic pain intensity scores over the past week of 6.8 ± 2.1 (0 to 10 scale), reflecting a high moderate to severe level of pain. Additionally, 87.9% noted that cannabis reduced their neuropathic pain intensity by more than 30%, and 92.3% reported that cannabis helped them to better deal with their neuropathic pain symptoms. Most participants (83.3%) also reported substituting their pain medications with cannabis, with the most substituted medication categories being opioids (47.0%), gabapentinoids (42.8%) and over-the-counter pain medications (42.2%). These preliminary results suggest that cannabis and cannabinoids may be effective in reducing neuropathic pain among those with SCI and may help to limit the need for certain pain medications.
Infantile orbital abscess caused by methicillin-resistant Staphylococcus aureus: a case report and literature review
Authors: Qin Yanran , Huo Junming , Liu Chengjun , Fu Yueqiang , Li Jing
Published: December 2023

Objective

To report and review infantile orbital abscess caused by methicillin-resistant Staphylococcus aureus (MRSA).

Methods

We report a case of MRSA-induced infantile orbital abscess accompanied by sepsis, pneumonia, and purulent meningitis. We systematically review cases of MRSA-induced infantile orbital abscess published in PubMed, Web of Science and ScienceDirect until April 2023.

Results

We reviewed 14 patients [our patient + 13 patients (10 papers) identified via literature searches]. There were nine boys and five girls; nine neonates and five older infants; and 8 full-term births and 1 preterm birth. The gestational age at birth was unknown for five infants. The right and left orbits were affected in 10 and 4 patients, respectively. The clinical presentation included periorbital soft-tissue edema or redness (11 patients), fever (7 patients), exophthalmos (10 patients), limited eye movement (4 patients), purulent eye secretions (2 patients), and skin abscess and convulsion (1 patient each). The source of infection was sinusitis (8 patients), vertical transmission, gingivitis, dacryocystitis, upper respiratory tract infection (1 patient each), and unknown (2 patients). MRSA was detected in blood (6 patients) or pus culture (8 patients). Vancomycin or linezolid were used for 11 patients; corticosteroids were administered to only 1 patient. Surgical drainage was performed for 13 infants (external drainage, 11 patients; endoscopic drainage, 2 patients). Two patients initially had pulmonary and intracranial infections. Except for one patient with neurological dysfunction at discharge, all other infants had no sequelae or complications.

Conclusion

Early aggressive anti-infective treatment and timely drainage are essential for managing MRSA-induced infantile orbital abscess.
Selective inhibitors targeting Fis1/Mid51 protein-protein interactions protect against hypoxia-induced damage in cardiomyocytes
Authors: Zerihun Mulate , Qvit Nir
Published: December 2023

Cardiovascular diseases (CVDs) are the most common non-communicable diseases globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Mitochondria play critical roles in cellular metabolic homeostasis, cell survival, and cell death, as well as producing most of the cell’s energy. Protein–protein interactions (PPIs) have a significant role in physiological and pathological processes, and aberrant PPIs are associated with various diseases, therefore they are potential drug targets for a broad range of therapeutic areas. Due to their ability to mimic natural interaction motifs and cover relatively larger interaction region, peptides are very promising as PPI inhibitors. To expedite drug discovery, computational approaches are widely used for screening potential lead compounds. Here, we developed peptides that inhibit mitochondrial fission 1 (Fis1)/mitochondrial dynamics 51 kDa (Mid51) PPI to reduce the cellular damage that can lead to various human pathologies, such as CVDs. Based on a rational design approach we developed peptide inhibitors of the Fis1/Mid51 PPI. In silico and in vitro studies were done to evaluate the biological activity and molecular interactions of the peptides. Two peptides, CVP-241 and CVP-242 were identified based on low binding energy and molecular dynamics simulations. These peptides inhibit Fis1/Mid51 PPI (-1324.9 kcal mol−1) in docking calculations (CVP-241, -741.3 kcal mol−1, and CVP-242, -747.4 kcal mol−1), as well as in vitro experimental studies Fis1/Mid51 PPI (KD 0.054 µM) Fis1/Mid51 PPI + CVP-241 (KD 3.43 µM), and Fis1/Mid51 PPI + CVP-242 (KD 44.58 µM). Finally, these peptides have no toxicity to H9c2 cells, and they increase cell viability in cardiomyocytes (H9c2 cells). Consequently, the identified inhibitor peptides could serve as potent molecules in basic research and as leads for therapeutic development.
Pharmacokinetics and bioavailability of a new long-acting insulin analog in healthy Chinese volunteers: an open, randomized, single-dose, two-period and two-sequence cross-over study
Authors: Chen Ke-Guang , Zhang Ye-Hui , Ye Pan-Pan , Gao Xue-Hu , Song Lin-Lin , Zhou Hai-Yan , Li Qian , Zhao Fu-Rong , Shi Jin-Yi , Yang Xin-Mei , Shen Kai , Feng Sheng , Zhao Wei
Published: December 2023

Objectives:INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T).

Methods:A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS/MS, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0–tand AUC0–∞) were used to evaluate relative bioavailability.

Results:After a single dose at 0.4 U/kg, the median Tmaxof INS068 was 12 h for both formulations, and the mean t1/2for T and R was 13.0 h and 12.6 h, respectively. The geometric means of Cmaxand AUC0–∞were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of Cmax, AUC0–tand AUC0–∞of T over R were 98.7% (90% CI: 92.7%–105.2%), 102.6% (90% CI: 100.0%–105.3%) and 102.8% (90% CI: 100.1%–105.5%).

Conclusion:The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials.

Clinical Trial Registration:clinicaltrials.gov, identifier: NCT05336071
An aqueous Commiphora myrrha extract ameliorates paclitaxel-induced peripheral neuropathic pain in mice
Authors: Al-Romaiyan Altaf , Barakat Ahmad , Jose Liny , Masocha Willias
Published: December 2023

Background: Chemotherapy-induced neuropathic pain (CINP) is a debilitating side effect in individuals undergoing cancer treatment. Treatment of CINP with the current available classes of drugs is limited and often yields unsatisfactory results. Finding therapeutic alternatives of plant origin could provide a new way for the management of CINP. Commiphora myrrha (CM) resin extract has been reported to have anti-inflammatory and analgesic activities, but the effect of CM on neuropathic pain is yet to be investigated in CINP.

Objectives: The aim of this study was to investigate the antinociceptive effect of CM extract in a mouse model of paclitaxel-induced neuropathic pain (PINP).

Methods: The effects of CM on thermal hyperalgesia and mechanical allodynia were assessed in female BALB/c mice with PINP using a hot plate and a plantar aesthesiometer, respectively. Motor coordination was evaluated using a rotarod apparatus. The involvement of transient receptor potential vanilloid channel 1 (TRPV1) in CM actions was investigated using a capsaicin (a TRPV1 agonist)-induced nociception test. The genetic expression of Trpv1, Nrf2, Sod2, and Hmox1 was assessed using real-time PCR, while protein expression of TRPV1, Iba-1, and CD11b was assessed using Wes™.

Results: Administration of CM to mice with established PINP produced a dose-dependent reduction in thermal hyperalgesia. Prophylactic treatment of mice with CM prevented the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia. CM did not change the motor coordination of mice, as the reaction latency and the rotational velocity of animals pretreated with CM extract were similar to those of animals pretreated with vehicle. CM significantly decreased the number and duration of the flick responses following capsaicin injection into the dorsal surface of the hind paw of mice. The protein expression of TRPV1 was upregulated in the spinal cord of paclitaxel-treated animals compared to vehicle-only-treated control animals, while CM-treated animals had values similar to vehicle-only-treated control animals. The mRNA expression of Nrf2, a major antioxidant transcription factor, was upregulated in the paw skin of mice treated with CM compared to those treated with paclitaxel alone.

Conclusion: These results indicate that CM may both treat established and prevent the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia without any impairment in the motor activity of mice. CM may mediate its action through the peripheral inhibition of TRPV1 channel activity, restoration of normal TRPV1 protein expression in the spinal cord, and elevation of cellular antioxidant defenses. CM has the potential to be used as a therapeutic alternative to treat CINP.
Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies
Authors: Mohamed Maged E. , El-Shafae Azza M. , Fikry Eman , Elbaramawi Samar S. , Elbatreek Mahmoud H. , Tawfeek Nora
Published: December 2023

Ulcerative colitis (UC) is an inflammatory bowel disease that is often resistant to current treatment options, leading to a need for alternative therapies. Herbal products have shown promise in managing various conditions, including UC. However, the potential of Casuarina glauca branchlets ethanolic extract (CGBRE) in treating UC has not been explored. This study aimed to analyze the chemical composition of CGBRE and evaluate its efficacy in UC treatment through in silico and in vivo experiments. LC-ESI-MS/MS was used to identify 86 compounds in CGBRE, with 21 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 171 potential UC targets for the bioactive compounds, including EGFR, LRRK2, and HSP90 as top targets, which were found to bind to key CGBRE compounds through molecular docking. Molecular docking findings suggested that CGBRE may be effective in the prevention or treatment of ulcerative colitis mediated by these proteins, where key CGBRE compounds exhibited good binding affinities through formation of numerous interactions. In vivo studies in rats with acetic acid-induced UC demonstrated that oral administration of 300 mg/kg CGBRE for 6 days reduced UC symptoms and colonic expression of EGFR, LRRK2, and HSP90. These findings supported the therapeutic potential of CGBRE in UC and suggested the need for further preclinical and clinical investigation.
Action-angle variables for the Lie–Poisson Hamiltonian systems associated with the Hirota–Satsuma modified Boussinesq equation
Authors: Geng Xue , Du Dianlou , Geng Xianguo
Published: December 2023

In this work, we present two finite-dimensional Lie–Poisson Hamiltonian systems associated with the Hirota–Satsuma modified Boussinesq equation by using the nonlinearization method. Moreover, the separation of variables on the common level set of Casimir functions is introduced to study these systems which are associated with a non-hyperelliptic algebraic curve. Finally, in light of the Hamilton–Jacobi theory, the action-angle variables for these systems are constructed, and the Jacobi inversion problem associated with the Hirota–Satsuma modified Boussinesq equation is obtained.