bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration
Authors: Anand Praveen , Privitera Rosario , Donatien Philippe , Fadavi Hassan , Tesfaye Solomon , Bravis Vassiliki , Misra V. Peter 
Published: October 2022

IntroductionCurrent oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., “disease modification.” We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy.Methods50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment.ResultsAt 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p = 0.02), and correlated with reduction in SF-MPQ overall pain score (p = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p = 0.0002) and NPDPN Q+SOC (p = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (p = 0.003) and NPDPN Q+SOC (p = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p = 0.0008) and GAP43 (p = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p = 0.006).ConclusionsCapsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.
Prediction of breast cancer-related lymphedema risk after postoperative radiotherapy via multivariable logistic regression analysis
Authors: Kim Jae Sik , Kim Jin Ho , Chang Ji Hyun , Kim Do Wook , Shin Kyung Hwan 
Published: October 2022

PurposeWe identified novel clinical and dosimetric prognostic factors affecting breast cancer-related lymphedema after postoperative radiotherapy (RT) and developed a multivariable logistic regression model to predict lymphedema in these patients.Methods and materialsIn total, 580 patients with unilateral breast cancer were retrospectively reviewed. All patients underwent breast surgery and postoperative RT with or without systemic treatment in 2015. Among the 580 patients, 532 with available RT plan data were randomly divided into training (n=372) and test (n=160) cohorts at a 7:3 ratio to generate and validate the lymphedema prediction models, respectively. An area under the curve (AUC) value was estimated to compare models.ResultsThe median follow-up duration was 5.4 years. In total, 104 (17.9%) patients experienced lymphedema with a cumulative incidence as follows: 1 year, 10.5%; 3 years, 16.4%; and 5 years, 17.6%. Multivariate analysis showed that body mass index ≥25 kg/m2 (hazard ratio [HR] 1.845), dissected lymph nodes ≥7 (HR 1.789), and taxane-base chemotherapy (HR 4.200) were significantly associated with increased lymphedema risk. Conversely, receipt of RT at least 1 month after surgery reduced the risk of lymphedema (HR 0.638). A multivariable logistic regression model using the above factors, as well as the minimum dose of axillary level I and supraclavicular lymph node, was created with an AUC of 0.761 and 0.794 in the training and test cohorts, respectively.ConclusionsOur study demonstrated that a shorter interval from surgery to RT and other established clinical factors were associated with increased lymphedema risk. By combining these factors with two dosimetric parameters, we propose a multivariable logistic regression model for breast cancer-related lymphedema prediction after RT.
Clinical significance of MMP-9 overexpression in endometrial cancer: A PRISMA-compliant meta-analysis
Authors: Li Xia , Zha Li , Li Bo , Sun Rong , Liu Jianhua , Zeng Hongwei 
Published: October 2022

ObjectiveSeveral studies have found that MMP-9, one of the extracellular matrix-degrading proteinases, was involved in EC’s (endometrial cancer) clinical progression and prognosis. However, the results involving the associations of MMP-9 expression with risk, clinical features and prognosis of EC were conflicting. Therefore, we performed a systematic review and meta-analysis to clarify the correlation of MMP-9 expression with EC.MethodsRelative studies involving the associations between MMP-9 expression and EC were retrieved from PubMed, Embase, Web of Science and CNKI (China National Knowledge Infrastructure) electronic databases. OR (odds ratio) with 95% CI (confidence interval) was applied to evaluate the associations of MMP-9 expression with risk and clinical features of EC. Furthermore, we evaluated the role of MMP-9 expression in prognosis of EC using HR and 95% CI. The funnel plots and Begg test were used to assess the publication bias.ResultsA total of 28 eligible studies were acquired from Pubmed, Embase, Web of science and CNKI databases. We found MMP-9 overexpression was significantly associated with the risk of EC (OR = 11.02, 95% CI = 7.51-16.16, P &lt; 0.05). In the meantime, MMP-9 overexpression was significantly associated with the tumor grade, FIGO stage, lymph node metastasis and myometrial invasion (Tumor grade: OR = 1.68, 95% CI = 1.09-2.58, P &lt; 0.05; FIGO stage: OR = 3.25, 95% CI = 1.73-6.08, P &lt; 0.05; Lymph node metastasis: OR = 2.98, 95% CI = 1.27-7.03, P &lt; 0.05; Myometrial invasion: OR = 2.42, 95% CI = 1.42-4.12, P &lt; 0.05) in Asians. In addition, the overall results showed that MMP-9 overexpression predicted a worse prognosis of EC (OR = 1.82, 95% CI = 1.01-2.62, P &lt; 0.05).ConclusionsMMP-9 overexpression might be a potential predictor of poor clinical progression and prognosis of EC.
High weekly integral dose and larger fraction size increase risk of fatigue and worsening of functional outcomes following radiotherapy for localized prostate cancer
Authors: Joseph Nuradh , Cicchetti Alessandro , McWilliam Alan , Webb Adam , Seibold Petra , Fiorino Claudio , Cozzarini Cesare , Veldeman Liv , Bultijnck Renée , Fonteyne Valérie , Talbot Christopher J. , Symonds Paul R. , Johnson Kerstie , Rattay Tim , Lambrecht Maarten , Haustermans Karin , De Meerleer Gert , Elliott Rebecca M. , Sperk Elena , Herskind Carsten , Veldwijk Marlon , Avuzzi Barbara , Giandini Tommaso , Valdagni Riccardo , Azria David , Jacquet Marie-Pierre Farcy , Charissoux Marie , Vega Ana , Aguado-Barrera Miguel E. , Gómez-Caamaño Antonio , Franco Pierfrancesco , Garibaldi Elisabetta , Girelli Giuseppe , Iotti Cinzia , Vavassori Vittotorio , Chang-Claude Jenny , West Catharine M. L. , Rancati Tiziana , Choudhury Ananya 
Published: October 2022

IntroductionWe hypothesized that increasing the pelvic integral dose (ID) and a higher dose per fraction correlate with worsening fatigue and functional outcomes in localized prostate cancer (PCa) patients treated with external beam radiotherapy (EBRT).MethodsThe study design was a retrospective analysis of two prospective observational cohorts, REQUITE (development, n=543) and DUE-01 (validation, n=228). Data were available for comorbidities, medication, androgen deprivation therapy, previous surgeries, smoking, age, and body mass index. The ID was calculated as the product of the mean body dose and body volume. The weekly ID accounted for differences in fractionation. The worsening (end of radiotherapy versus baseline) of European Organisation for Research and Treatment of Cancer EORTC) Quality of Life Questionnaire (QLQ)-C30 scores in physical/role/social functioning and fatigue symptom scales were evaluated, and two outcome measures were defined as worsening in ≥2 (WS2) or ≥3 (WS3) scales, respectively. The weekly ID and clinical risk factors were tested in multivariable logistic regression analysis.ResultsIn REQUITE, WS2 was seen in 28% and WS3 in 16% of patients. The median weekly ID was 13.1 L·Gy/week [interquartile (IQ) range 10.2-19.3]. The weekly ID, diabetes, the use of intensity-modulated radiotherapy, and the dose per fraction were significantly associated with WS2 [AUC (area under the receiver operating characteristics curve) =0.59; 95% CI 0.55-0.63] and WS3 (AUC=0.60; 95% CI 0.55-0.64). The prevalence of WS2 (15.3%) and WS3 (6.1%) was lower in DUE-01, but the median weekly ID was higher (15.8 L·Gy/week; IQ range 13.2-19.3). The model for WS2 was validated with reduced discrimination (AUC=0.52 95% CI 0.47-0.61), The AUC for WS3 was 0.58,ConclusionIncreasing the weekly ID and the dose per fraction lead to the worsening of fatigue and functional outcomes in patients with localized PCa treated with EBRT.
The ventilatory response to hypoxia is blunted in some preterm infants during the second year of life
Authors: Freislich Zoe , Stoecklin Benjamin , Hemy Naomi , Pillow J. Jane , Hall Graham L. , Wilson Andrew C. , Simpson Shannon J. 
Published: October 2022

BackgroundPreterm birth and subsequent neonatal ventilatory treatment disrupts development of the hypoxic ventilatory response (HVR). An attenuated HVR has been identified in preterm neonates, however it is unknown whether the attenuation persists into the second year of life. We investigated the HVR at 12–15 months corrected postnatal age and assessed predictors of a blunted HVR in those born very preterm (&lt;32 weeks gestation).MethodsHVR was measured in infants born very preterm. Hypoxia was induced with a three-step reduction in their fraction of inspired oxygen (FIO2) from 0.21 to 0.14. Respiratory frequency (f), tidal volume (VT), minute ventilation (VE), inspiratory time (tI), expiratory time (tE), VT/tI, tI/tTOT, VT/tTOT, area under the low-volume loop and peak tidal expiratory flow (PTEF) were measured at the first and third minute of each FIO2. The change in respiratory variables over time was assessed using a repeated measures ANOVA with Greenhouse-Geisser correction. A blunted HVR was defined as a &lt;10% rise in VE, from normoxia. The relationship between neonatal factors and the magnitude of HVR was assessed using Spearman correlation.ResultsThirty nine infants born very preterm demonstrated a mean (SD) HVR of 11.4 (10.1)% (increase in VE) in response to decreasing FIO2 from 0.21 to 0.14. However, 17 infants (44%) failed to increase VE by ≥10% (range −14% to 9%) and were considered to have a blunted response to hypoxia. Males had a smaller HVR than females [ΔVE (−9.1%; −15.4, −2.8; p = 0.007)].ConclusionInfants surviving very preterm birth have an attenuated ventilatory response to hypoxia that persists into the second year of life, especially in males.
Effects of Broussonetia papyrifera (L.) L'Hér. ex Vent. fruits water extract on hippocampal neurogenesis in the treatment of APP/PS1 transgenic mice
Authors: Yan Yu-hui , Huang Zi-han , Xiong Qing-ping , Song Yue-wen , Li Si-yang , Yang Bao-wei , Sun Lan , Zhang Meng-yuan , Ji Yu 
Published: October 2022

Background: Adult neurogenesis plays an important role in repairing damaged neurons and improving cognitive impairment in Alzheimer’s disease (AD). B. Papyrifera (L.) L'Hér. ex Vent. fruits (BL), a traditional Chinese medicine for tonifying the kidney, has been reported to improve cognitive function in AD mice, but the underlying mechanisms have not been clearly illuminated. This study aimed to provide an overview of the differential compounds in the brain of APP/PS1 mice after BL water extract (BLWE) treatment through metabolomics technology and to elucidate whether the therapeutic effect and mechanism are through the enhancement of neurogenesis.Methods: APP/PS1 transgenic mice were treated with different doses of BLWE. After 6 weeks of intragastric injection, the therapeutic effects of BLWE on APP/PS1 transgenic mice were determined by the Morris water maze test, immunohistochemistry, hematoxylin &amp; eosin and Nissl staining, enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Subsequently, metabolomics technology was used to analyze the regulatory effect of BLWE on differential compounds in the brain of APP/PS1 mice, and on this basis, its molecular mechanism of BLWE was screened. Finally, the protein expression of the Wnt/β-catenin signaling pathway was detected by Western blotting.Results: After BLWE treatment, the learning and memory function of APP/PS1 mice were significantly improved, which was related to the increase in the number of Nestin+/BrdU+ and NeuN+/BrdU+ cells, and the decrease in the number of apoptotic cells in the hippocampus. BLWE treatment could also up-regulate the expression of synapse-associated proteins. Moreover, BLWE could modulate endogenous metabolic compounds in the brains of AD mice, including N-acetyl-aspartate, glutamine, etc. Furthermore, BLWE inhibited the phosphorylation of Tyr216-GSK-3β and β-catenin protein while increased CyclinD1 protein expression.Conclusion: We demonstrated that BLWE can enhance neural stem cells proliferation and improve neurogenesis, thereby efficiently repairing damaged neurons in the hippocampus and ameliorating cognitive impairment in APP/PS1 transgenic mice. The mechanism is at least partly through activating the Wnt/β-catenin signaling pathway.
Stb6 mediates stomatal immunity, photosynthetic functionality, and the antioxidant system during the Zymoseptoria tritici-wheat interaction
Authors: Ghiasi Noei Fateme , Imami Mojtaba , Didaran Fardad , Ghanbari Mohammad Amin , Zamani Elham , Ebrahimi Amin , Aliniaeifard Sasan , Farzaneh Mohsen , Javan-Nikkhah Mohammad , Feechan Angela , Mirzadi Gohari Amir 
Published: October 2022

This study offers new perspectives on the biochemical and physiological changes that occur in wheat following a gene-for-gene interaction with the fungal pathogen Zymoseptoria tritici. The Z. tritici isolate IPO323, carries AvrStb6, while ΔAvrStb6#33, lacks AvrStb6. The wheat cultivar (cv.) Shafir, bears the corresponding resistance gene Stb6. Inoculation of cv. Shafir with these isolates results in two contrasted phenotypes, offering a unique opportunity to study the immune response caused by the recognition of AvrStb6 by Stb6. We employed a variety of methodologies to dissect the physiological and biochemical events altered in cv. Shafir, as a result of the AvrStb6-Stb6 interaction. Comparative analysis of stomatal conductance demonstrated that AvrStb6-Stb6 mediates transient stomatal closures to restrict the penetration of Zymoseptoria tritici. Tracking photosynthetic functionality through chlorophyll fluorescence imaging analysis demonstrated that AvrStb6-Stb6 retains the functionality of photosynthesis apparatus by promoting Non-Photochemical Quenching (NPQ). Furthermore, the PlantCV image analysis tool was used to compare the H2O2 accumulation and incidence of cell death (2, 4, 8, 12, 16, and 21 dpi), over Z. tritici infection. Finally, our research shows that the AvrStb6-Stb6 interaction coordinates the expression and activity of antioxidant enzymes, both enzymatic and non-enzymatic, to counteract oxidative stress. In conclusion, the Stb6-AvrStb6 interaction in the Z. tritici-wheat pathosystem triggers transient stomatal closure and maintains photosynthesis while regulating oxidative stress.
Greening or browning? The macro variation and drivers of different vegetation types on the Qinghai-Tibetan Plateau from 2000 to 2021
Authors: Wang Huihui , Zhan Jinyan , Wang Chao , Liu Wei , Yang Zheng , Liu Huizi , Bai Chunyue 
Published: October 2022

Vegetation greenness is one of the main indicators to characterize changes in terrestrial ecosystems. China has implemented a few large-scale ecological restoration programs on the Qinghai-Tibetan Plateau (QTP) to reverse the trend of ecosystem degradation. Although the effectiveness of these programs is beginning to show, the mechanisms of vegetation degradation under climate change and human activities are still controversial. Existing studies have mostly focused on changes in overall vegetation change, with less attention on the drivers of change in different vegetation types. In this study, earth satellite observation records were used to robustly map changes in vegetation greenness on the QTP from 2000 to 2021. The random forest (RF) algorithm was further used to detect the drivers of greenness browning on the QTP as a whole and in seven different vegetation types. The results show that an overall trend of greening in all seven vegetation types on the QTP over a 21-year period. The area of greening was 46.54×104 km2, and browning was 5.32×104 km2, representing a quarter and 2.86% of the natural vegetation area, respectively. The results of the browning driver analysis show that areas with high altitude, reduced annual precipitation, high intensity of human activity, average annual maximum and average annual minimum precipitation of approximately 500 mm are most susceptible to browning on the QTP. For the seven different vegetation types, their top 6 most important browning drivers and the ranking of drivers differed. DEM and precipitation changes are important drivers of browning for seven vegetation types. These results reflect the latest spatial and temporal dynamics of vegetation on the QTP and highlight the common and characteristic browning drivers of vegetation ecosystems. They provide support for understanding the response of different vegetation to natural and human impacts and for further implementation of site-specific restoration measures.
Assessment of knowledge and attitude of healthcare professionals regarding the use of telemedicine: A cross-sectional study from rural areas of Sindh, Pakistan
Authors: Kumar Grouve , Shardha Harsha Komal , Tariq Waleed , Qazi Mansoor Ahmed , Kumar Kantesh , Maheshwari Chandni , Hussain Atif , Tahir Muhammad Junaid , Bai Jharna , Asghar Muhammad Sohaib 
Published: October 2022

BackgroundTelemedicine has proved its significance in the healthcare system, especially during the coronavirus disease 2019 (COVID-19) pandemic as it assists in the provision of early and effective healthcare to those in distant areas. This study aimed to assess the knowledge and attitude of healthcare professionals toward the use of telemedicine in the rural areas of Sindh, Pakistan.Materials and methodsThe cross-sectional study was conducted with 212 healthcare professionals including physicians, consultants, surgeons, residents, dentists, and house officers working in public sector hospitals. The face-to-face method was used for data collection. Chi-square test and logistic regression analysis were applied to find the association between different variables and knowledge and practice of telemedicine using SPSS V 24.ResultsThe knowledge of participants regarding the usability of telemedicine and various tools used for the provision of medical services (video consultations, conferencing, use of applications, software, and online groups) was good. A total of 52.2% of participants showed agreement when they were questioned about being aware of online healthcare service provision. In this study, 52.8% of the participants practiced telemedicine by delivering healthcare services through online consultations. The majority of the participants were surgeons (25.9%), residents (23.1%), and physicians (18.9%). The internet (42.4%) and public media (25.9%) were the major sources of information for telemedicine. A total of 70.5% of participants suggested that strategies and efforts should be directed toward the enhanced implementation of telemedicine. Training in telemedicine as a source of information [OR = 13.02 (95% CI = 3.9–43.6), p &lt; 0.001)] and awareness regarding the effect of telemedicine in healthcare quality [OR = 10.25 (95% CI = 2.9–35.4), p &lt; 0.001)] remained the predicting factors for the practice of telemedicine among healthcare workers using multivariate regression analysis.ConclusionTelemedicine has technologically revolutionized the medical sciences worldwide. The awareness level and usage of telemedicine were good among healthcare professionals in rural Sindh. Telemedicine should be utilized to provide quality healthcare in underprivileged areas by investing in infrastructure and education.
Chemical and Biological Activity Profiling of Hedyosmum strigosum Todzia Essential Oil, an Aromatic Native Shrub from Southern Ecuador
Authors: Cartuche Luis , Calva James , Valarezo Eduardo , Chuchuca Nayeli , Morocho Vladimir 
Published: October 2022

The present study aimed to determine the chemical composition, enantiomeric distribution and the biological profile of Hedyosmum strigosum essential oil (EO). The antioxidant properties and anticholinesterase effect were measured by spectroscopic methods and antimicrobial potency assessed against 8 bacteria and two fungi. H. strigosum is a native shrub, particularly found in Ecuador and Colombia at 2000 to 3500 m a.s.l. Chemical composition was determined by GC-MS and GC-FID. A total of 44 compounds were detected, representing more than 92% of the EO composition. The main compounds were thymol (24.35, 22.48%), α-phellandrene (12.15, 13.93%), thymol acetate (6.59, 9.39%) and linalool (8.73, 5.82%), accounting for more than 51% of the EO. The enantioselective analysis revealed the presence of 5 pure enantiomers and 3 more as a racemic mixture. The EO exerted a strong antioxidant capacity, determined by ABTS assay, with a SC50 of 25.53 µg/mL and a strong and specific antimicrobial effect against Campylobacter jejuni with a MIC value of 125 µg/mL. A moderate acetylcholinesterase inhibitory effect was also observed with an IC50 value of 137.6 µg/mL. To the best of our knowledge this is the first report of the chemical composition and biological profile of H. strigosum EO.