bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of Methyltransferase-like 3-Mediated RNA N6-Methyladenosine Exacerbates the Development of Psoriasis Vulgaris in Imiquimod-Induced Psoriasis-like Mouse Model
Authors: Wang Yanan , Huang Jiuzuo , Jin Hongzhong
Published: October 2022

N6-methyladenosine (m6A) methylation is the most pervasive and intensively studied mRNA modification, which regulates gene expression in different physiological processes, such as cell proliferation, differentiation, and inflammation. Studies of aberrant m6A in human diseases such as cancer, obesity, infertility, neuronal disorders, immune diseases, and inflammation are rapidly evolving. However, the regulatory mechanism and physiological significance of m6A methylation in psoriasis vulgaris are still poorly understood. In this study, we found that m6A methylation and Methyltransferase-like 3 (METTL3) were both downregulated in psoriatic skin lesions and were negatively correlated with Psoriasis Area and Severity Index (PASI) scores. Inhibiting m6A methylation by knocking down Mettl3 promoted the development of psoriasis and increased its severity in imiquimod-induced psoriasis-like model mice. Our results indicate a critical role of METTL3- mediated m6A methylation in the pathogenesis of psoriasis vulgaris.
Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury
Authors: Abu-Tayeh Suleiman Hanan , Said Shereen , Ali Saleh Haya , Gamliel-Lazarovich Aviva , Haddad Eyas , Minkov Irina , Zohar Yaniv , Ilan Neta , Vlodavsky Israel , Abassi Zaid , Assady Suheir
Published: October 2022

The kidney glomerular filtration barrier (GFB) is enriched with heparan sulfate (HS) proteoglycans, which contribute to its permselectivity. The endoglycosidase heparanase cleaves HS and hence appears to be involved in the pathogenesis of kidney injury and glomerulonephritis. We have recently reported, nonetheless, that heparanase overexpression preserved glomerular structure and kidney function in an experimental model of Adriamycin-induced nephropathy. To elucidate mechanisms underlying heparanase function in podocytes—key GFB cells, we utilized a human podocyte cell line and transgenic mice overexpressing heparanase. Notably, podocytes overexpressing heparanase (H) demonstrated significantly higher survival rates and viability after exposure to Adriamycin or hydrogen peroxide, compared with mock-infected (V) podocytes. Immunofluorescence staining of kidney cryo-sections and cultured H and V podocytes as well as immunoblotting of proteins extracted from cultured cells, revealed that exposure to toxic injury resulted in a significant increase in autophagic flux in H podocytes, which was reversed by the heparanase inhibitor, Roneparstat (SST0001). Heparanase overexpression was also associated with substantial transcriptional upregulation of autophagy genes BCN1, ATG5, and ATG12, following Adriamycin treatment. Moreover, cleaved caspase-3 was attenuated in H podocytes exposed to Adriamycin, indicating lower apoptotic cell death in H vs. V podocytes. Collectively, these findings suggest that in podocytes, elevated levels of heparanase promote cytoprotection.
Brain Effects of SC-Nanophytosomes on a Rotenone-Induced Rat Model of Parkinson’s Disease—A Proof of Concept for a Mitochondria-Targeted Therapy
Authors: Mendes Daniela , Peixoto Francisco , Oliveira Maria Manuel , Andrade Paula Branquinho , Videira Romeu António
Published: October 2022

Mitochondria are an attractive target to fight neurodegenerative diseases due to their important functions for cells and the particularly close relationship between the functional connectivity among brain regions and mitochondrial performance. This work presents a mitochondria-targeted therapy designed to modulate the functionality of the mitochondrial respiratory chain and lipidome, parameters that are affected in neurodegeneration, including in Parkinson’s disease (PD). This therapy is supported by SC-Nanophytosomes constructed with membrane polar lipids, from Codium tomentosum, and elderberry anthocyanin-enriched extract, from Sambucus nigra L. SC-Nanophytosomes are nanosized vesicles with a high negative surface charge that preserve their properties, including anthocyanins in the flavylium cation form, under conditions that mimic the gastrointestinal tract pH changes. SC-Nanophytosomes, 3 µM in phospholipid, and 2.5 mg/L of EAE-extract, delivered by drinking water to a rotenone-induced PD rat model, showed significant positive outcomes on disabling motor symptoms associated with the disease. Ex vivo assays were performed with two brain portions, one comprising the basal ganglia and cerebellum (BG-Cereb) and the other with the cerebral cortex (C-Cortex) regions. Results showed that rotenone-induced neurodegeneration increases the α-synuclein levels in the BG-Cereb portion and compromises mitochondrial respiratory chain functionality in both brain portions, well-evidenced by a 50% decrease in the respiratory control rate and up to 40% in complex I activity. Rotenone-induced PD phenotype is also associated with changes in superoxide dismutase and catalase activities that are dependent on the brain portion. Treatment with SC-Nanophytosomes reverted the α-synuclein levels and antioxidant enzymes activity to the values detected in control animals. Moreover, it mitigated mitochondrial dysfunction, with positive outcomes on the respiratory control rate, the activity of individual respiratory complexes, and the fatty acid profile of the membrane phospholipids. Therefore, SC-Nanophytosomes are a promising tool to support mitochondria-targeted therapy for neurodegenerative diseases.
Effects of Sub-Minimum Inhibitory Concentrations of Imipenem and Colistin on Expression of Biofilm-Specific Antibiotic Resistance and Virulence Genes in Acinetobacter baumannii Sequence Type 1894
Authors: Shenkutie Abebe Mekuria , Zhang Jiaying , Yao Mianzhi , Asrat Daniel , Chow Franklin W. N. , Leung Polly H. M.
Published: October 2022

Antibiotics at suboptimal doses promote biofilm formation and the development of antibiotic resistance. The underlying molecular mechanisms, however, were not investigated. Here, we report the effects of sub-minimum inhibitory concentrations (sub-MICs) of imipenem and colistin on genes associated with biofilm formation and biofilm-specific antibiotic resistance in a multidrug-tolerant clinical strain of Acinetobacter baumannii Sequence Type (ST) 1894. Comparative transcriptome analysis was performed in untreated biofilm and biofilm treated with sub-MIC doses of imipenem and colistin. RNA sequencing data showed that 78 and 285 genes were differentially expressed in imipenem and colistin-treated biofilm cells, respectively. Among the differentially expressed genes (DEGs), 48 and 197 genes were upregulated exclusively in imipenem and colistin-treated biofilm cells, respectively. The upregulated genes included those encoding matrix synthesis (pgaB), multidrug efflux pump (novel00738), fimbrial proteins, and homoserine lactone synthase (AbaI). Upregulation of biofilm-associated genes might enhance biofilm formation when treated with sub-MICs of antibiotics. The downregulated genes include those encoding DNA gyrase (novel00171), 30S ribosomal protein S20 (novel00584), and ribosome releasing factor (RRF) were downregulated when the biofilm cells were treated with imipenem and colistin. Downregulation of these genes affects protein synthesis, which in turn slows down cell metabolism and makes biofilm cells more tolerant to antibiotics. In this investigation, we also found that 5 of 138 small RNAs (sRNAs) were differentially expressed in biofilm regardless of antibiotic treatment or not. Of these, sRNA00203 showed the highest expression levels in biofilm. sRNAs regulate gene expression and are associated with biofilm formation, which may in turn affect the expression of biofilm-specific antibiotic resistance. In summary, when biofilm cells were exposed to sub-MIC doses of colistin and imipenem, coordinated gene responses result in increased biofilm production, multidrug efflux pump expression, and the slowdown of metabolism, which leads to drug tolerance in biofilm. Targeting antibiotic-induced or repressed biofilm-specific genes represents a new strategy for the development of innovative and effective treatments for biofilm-associated infections caused by A. baumannii.
Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients
Authors: van de Weerd Simone , Smit Marloes A. , Roelands Jessica , Mesker Wilma E. , Bedognetti Davide , Kuppen Peter J. K. , Putter Hein , Tollenaar Rob A. E. M. , Roodhart Jeanine M. L. , Hendrickx Wouter , Medema Jan Paul , van Krieken J. Han J. M.
Published: October 2022

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.
Clinical Efficacies of FLT3 Inhibitors in Patients with Acute Myeloid Leukemia
Authors: Song Moo-Kon , Park Byeong-Bae , Uhm Ji-Eun
Published: October 2022

FLT3 mutations are the most common genomic alteration detected in acute myeloid leukemia (AML) with a worse clinical prognosis. The highly frequent FLT3 mutations, together with the side effects associated with clinical prognosis, make FLT3 promising treatment targets and have provoked the advancement of FLT3 inhibitors. Recently, numerous FLT3 inhibitors were actively developed, and thus the outcomes of this aggressive subtype of AML were significantly improved. Recently, midostaurin and gilteritinib were approved as frontline treatment of AML and as therapeutic agents in the recurred disease by the United States Food and Drug Administration. Recently, numerous promising clinical trials attempted to seek appropriate management in frontline settings, in relapsed/refractory disease, or after stem cell transplantation in AML. This review follows numerous clinical trials about the usefulness of FLT3 inhibitors as frontline therapy, as relapsed/refractory conditioning, and as maintenance therapy of stem cell transplantation. The cumulative data of FLT3 inhibitors would be important clinical evidence for further management with FLT3 inhibitors in AML patients with FLT3 mutations.
Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens
Authors: Oku Yusuke , Madia Federica , Lau Pierre , Paparella Martin , McGovern Timothy , Luijten Mirjam , Jacobs Miriam N.
Published: October 2022

With recent rapid advancement of methodological tools, mechanistic understanding of biological processes leading to carcinogenesis is expanding. New approach methodologies such as transcriptomics can inform on non-genotoxic mechanisms of chemical carcinogens and can be developed for regulatory applications. The Organisation for the Economic Cooperation and Development (OECD) expert group developing an Integrated Approach to the Testing and Assessment (IATA) of Non-Genotoxic Carcinogens (NGTxC) is reviewing the possible assays to be integrated therein. In this context, we review the application of transcriptomics approaches suitable for pre-screening gene expression changes associated with phenotypic alterations that underlie the carcinogenic processes for subsequent prioritisation of downstream test methods appropriate to specific key events of non-genotoxic carcinogenesis. Using case studies, we evaluate the potential of gene expression analyses especially in relation to breast cancer, to identify the most relevant approaches that could be utilised as (pre-) screening tools, for example Gene Set Enrichment Analysis (GSEA). We also consider how to address the challenges to integrate gene panels and transcriptomic assays into the IATA, highlighting the pivotal omics markers identified for assay measurement in the IATA key events of inflammation, immune response, mitogenic signalling and cell injury.
Cyclosporin A as a Potential Insecticide to Control the Asian Corn Borer Ostrinia furnacalis Guenée (Lepidoptera: Pyralidae)
Authors: Sun Chengxian , Li Shunjia , Wang Kai , Yin Xinming , Wang Yanmei , Du Mengfang , Wei Jizhen , An Shiheng
Published: October 2022

The long-term use of chemical insecticides has caused serious problems of insect resistance and environmental pollution; new insecticides are needed to solve this problem. Cyclosporin A (CsA) is a polypeptide produced by many fungi, which is used to prevent or treat immune rejection during organ transplantation. However, little is known about the utility of CsA as an insecticide. Therefore, this study evaluated the insecticidal activity of CsA using Ostrinia furnacalis as a model. The results demonstrated that CsA was toxic to O. furnacalis with LC50 values of 113.02 μg/g and 198.70 μg/g for newly hatched neonates and newly molted third-instar larvae, respectively. Furthermore, CsA treatment had sublethal effects on the development of O. furnacalis, and significantly reduced the fecundity of adults; this suggests that CsA has great potential to suppress O. furnacalis populations. Further analysis revealed that CsA suppressed calcineurin activity in larvae. CsA had independent or synergistic toxic effects on O. furnacalis when combined with β-cypermethrin, indoxacarb, emamectin benzoate, azadirachtin, and the Bacillus thuringiensis toxin Cry1Ac, which suggests that CsA can help prevent or manage resistance. Our study provides detailed information on the potential of CsA as an insecticide for controlling lepidopterans.
The Role of Tire Leachate in Condition-Specific Competition and the Persistence of a Resident Mosquito from a Competitively Superior Invader
Authors: Villena Oswaldo , Sullivan Joseph , Landa Edward , Yarwood Stephanie , Torrents Alba , Zhang Aijun , Leisnham Paul
Published: October 2022

(1) Background: Condition-specific competition, when the outcome of competition varies with abiotic conditions, can facilitate species coexistence in spatially or temporally variable environments. Discarded vehicle tires degrade to leach contaminants into collected rainwater that provide habitats for competing mosquito species. We tested the hypothesis that more highly degraded tires that contain greater tire leachate alters interspecific mosquito competition to produce a condition-specific advantage for the resident, Culex pipiens, by altering the outcome of competition with the competitively superior invasive Aedes albopictus. (2) Methods: In a competition trial, varying densities of newly hatched Ae. albopictus and Cx. pipiens larvae were added to tires that had been exposed to three different ultraviolet (UV)-B conditions that mimicked full-sun, shade, or no UV-B conditions in the field. We also measured Cx. pipiens and Ae. albopictus oviposition preference among four treatments with varying tire leachate (high and low) and resources (high and low) amounts to determine if adult gravid females avoided habitats with higher tire leachate. (3) Results: We found stronger competitive effects of Cx. pipiens on the population performance and survival of Ae. albopictus in tires exposed to shade and full-sun conditions that had higher concentrations of contaminants. Further, zinc concentration was higher in emergent adults of Ae. albopictus than Cx. pipiens. Oviposition by these species was similar between tire leachate treatments but not by resource amount. (4) Conclusions: These results suggest that degraded tires with higher tire leachate may promote condition-specific competition by reducing the competitive advantage of invasive Ae. albopictus over resident Cx. pipiens and, combined with Cx. pipiens’ preferential oviposition in higher resource sites, contribute to the persistence of the resident species.
Wound-Healing Effect of Antheraea pernyi Epidermal Growth Factor
Authors: Piao Yu-Lan , Zhang Chun-Yang , Zhang Yue , Qian Kun , Zhou Ying , Liu Jun-Yan , Chang Young-Cheol , Cho Hoon , Choi Dubok
Published: October 2022

To evaluate the wound-healing effect of Antheraea pernyi epidermal growth factor (ApEGF), we performed the sequence analysis, cloning, and prokaryotic expression of cDNA from the ApEGF gene, examined the transcriptional changes, and investigated the wound-healing effect of this protein in cells and rat epidermis. Primers were designed based on available sequence information related to the ApEGF gene in a public database, and part of the ApEGF sequence was obtained. The full-length cDNA sequence of ApEGF was obtained using inverse PCR. The gene sequence fragment of ApEGF was 666 bp in length, encoding 221 amino acids, with a predicted protein mass of 24.19 kD, an isoelectric point of 5.15, and no signal peptide sequence. Sequence homology analysis revealed 86.1% sequence homology with Bombyx mori, 92.7% with Manducal sexta, 92.6% with Trichoplusia ni, and 91.8% with Helicoverpa armigera. ApEGF was truncated and then subjected to prokaryotic expression, isolation, and purification. Truncated ApEGF was used for wound-healing experiments in vitro and in vivo. The results showed that after 48 h, transforming growth factor (TGF)-β1 had 187.32% cell growth effects, and the ApEGF group had 211.15% cell growth compared to the control group in vitro. In rat epidermis, truncated ApEGF showed a significantly better healing effect than the control. This result indicated that ApEGF, which exerted a direct wound-healing effect, could be used in wound-healing therapy.
Post-Intensive Care Syndrome after Critical Illness: An Imperative for Effective Prevention
Authors: Paul Nicolas , Weiss Björn
Published: October 2022

Over the last decades, the importance of intensive care has considerably increased [...]
A Retrospective Taiwanese-Population-Based Clinical Study on Determining the Efficacy and Safety of Disposable Circumcision Anastomat
Authors: Chou An-Chi , Laih Chun-Yo , Ku Fang-Yu
Published: October 2022

Traditional approaches for male circumcision are tedious and could lead to complications such as peri-/postoperative pain, bleeding, and infection. Thus, for the first time, we investigated the surgical outcomes of recently the discovered Disposable Circumcision Anastomat Type A (Dongguan ZSR Biomedical Technology Company Ltd., China), a disposable circumcision suture device (DCSD), in terms of the operation time, surgical complexity, safety, satisfaction, and aesthetic outcomes and most importantly the prognostic factors for postoperative infection. A total of 394 individuals were circumcised, with a mean age, body mass index (BMI), stretched penile length (SPL), and penile circumference of 30.1 ± 7.05 years, 25.47 ± 4.73, 10.12 ± 1.61, and 7 ± 0.73 cm, respectively. Associated comorbidities included diabetes mellitus (6.09%), hypertension (2.03%), gout (1.02%), end-stage renal disease (ESRD, 0.25%), and HIV (0.25%). The mean operation time, average postoperative bleeding, and wound infection rate was 31.4 ± 9.96 min, 2.54%, and 9.39%, respectively. The mean VAS postoperative pain scores at D0 and D1 were 4.4 ± 2.4 and 1.9 ± 1.6, respectively. Moreover, 1.27% of subjects required reoperation, and a 2.03% rate of instrument malfunction was noted. The significant factors associated with the post-operative infection group were age (p = 0.0313), BW (p = 0.0081), BMI (p = 0.0026), penile circumference (p = 0.0343), and DM (p ≤ 0.001). Multivariate analyses revealed only DM as a statistically significant factor (p < 0.001). Our box–whisker plot revealed no significant difference between the HbA1c level of infection (Hb1Ac = 7.77 ± 1.39) and non-infection groups (Hb1Ac = 6.92 ± 1.84). However, a trend of higher glycemic index in the infection group was observed. Conclusively, DSCD could be an effective and safe alternative to performing circumcision. However, in the population with advanced aging, phimosis, elevated BMI, and DM (HbA1C > 9%), users should be highly cautious due to the increased risk of infection, dehiscence, and hematoma.
Endoscopic Ultrasound-Guided Botox Injection for Refractory Anal Fissure
Authors: Randhawa Navkiran , Khalyfa Ahamed , Aslam Rida , Roebuck M. Christopher , Inam Mahnoor , Ayub Kamran
Published: October 2022

Background: Anal fissures cause severe pain and can be difficult to treat. Medical therapy is initially used, followed by sigmoidoscopy-guided botox injections if the medical therapy is not successful. With this technique, however, it is not clear whether botox is injected into the muscle layer or submucosa. Aim: To evaluate the efficacy of EUS-guided botox injection directly into the internal sphincter. Methods: Consecutive patients with chronic anal fissure refractory to conventional endoscopic botulinum toxin type A injection were enrolled in the study. EUS was performed using a linear array echoendoscope, and a 25 G needle was used to inject botox. All patients were followed up at one- and two-month intervals. Results: Eight patients with chronic anal fissures were included in the study. Six patients had an excellent response to botox at the two-month interval using a visual analog pain scale, while one patient had a moderate response with a pain score reduction of 40%. One patient had no response. No complications were noted. An improvement in visual analog scale (pre-score > post-score) was statistically significant at the p < 0.01 level. Conclusion: EUS-guided botox injection into the internal sphincter appears to be a promising technique for patients with refractory anal fissure with pain.
Predictive Factors for Failure of Intraarticular Injection in Management of Adhesive Capsulitis of the Shoulder
Authors: Hanish Stefan J. , Resnick Mathew L. , Kim Hyunmin M. , Smith Matthew J.
Published: October 2022

Intraarticular (IA) corticosteroid injections have been demonstrated to be an effective management for adhesive capsulitis in both the short- and mid-term. Yet, certain patients fail to improve both subjectively and clinically. This study aims to identify predictive factors for treatment failure of IA injections in management of adhesive capsulitis. A retrospective review found 533 patients undergoing IA corticosteroid or IA NSAID injection for adhesive capsulitis between June 2015 and May 2020 at a single healthcare institution. Patient demographics characteristics, comorbidities, pain scores, and range of motion were compared. Treatment failure was defined as need for subsequent IA injection within 6 months or progression to surgical management within 12 months. 152 patients (28.52%) experienced treatment failure of IA corticosteroid injection. Pre-injection pain scores were greater for those who experienced treatment failure (5.40 vs. 4.21, p < 0.05). Post-injection pain scores were greater for those who experienced treatment failure (3.77 vs. 2.17, p < 0.01). Reduced post-injection external rotation in abduction also predicted treatment failure (56.88° vs. 70.22°, p < 0.01). IA corticosteroid injections are associated with increased rates of failure and progression to surgical management when patients present with increased pain levels as well as with less improvement in pain levels and ROM following injection.
The Interactive Effects of Post-Traumatic Stress Symptoms and Breathlessness on Fatigue Severity in Post-COVID-19 Syndrome
Authors: Harenwall Sari , Heywood-Everett Suzanne , Henderson Rebecca , Smith Joanne , McEnery Rachel , Bland Amy R.
Published: October 2022

Background: Post-traumatic stress symptoms (PTSS) and breathlessness have been well documented in the acute phase of COVID-19 as well as in Post-COVID-19 Syndrome (PCS), commonly known as Long-COVID. The present study aimed to explore whether PTSS and breathlessness interact to exacerbate fatigue among individuals recovering from PCS, similar to the effects evidenced in other health conditions that feature respiratory distress.. Methods: Outcome measures were collected from 154 participants reporting persistent fatigue following acute COVID-19 infection who were enrolled in a 7-week rehabilitation course provided by the Primary Care Wellbeing Service (PCWBS) in Bradford District Care NHS Foundation Trust (BDCFT). Results: Hierarchical multiple linear regression revealed that fatigue severity was associated with a significant interaction between PTSS and breathlessness, even when controlling for pre-COVID health related quality of life (HRQoL), age, symptom duration and hospital admittance during the acute phase. Furthermore, improvements in fatigue following rehabilitation were significantly associated with improvements in PTSS. Conclusions: PTSS may be an important therapeutic target in multidisciplinary rehabilitation for reducing fatigue in the recovery from PCS. It is therefore important that treatment for PCS takes a biopsychosocial approach to recovery, putting emphasis on direct and indirect psychological factors which may facilitate or disrupt physical recovery. This highlights the need for all PCS clinics to screen for PTSD and if present, target as a priority in treatment to maximise the potential for successful rehabilitation.
Multimodal Treatment with Cognitive Behavioral Therapeutic Intervention Plus Bladder Treatment Is More Effective than Monotherapy for Patients with Interstitial Cystitis/Bladder Pain Syndrome—A Randomized Clinical Trial
Authors: Yu Wan-Ru , Jhang Jia-Fong , Chen Bai-Yueh , Ou Syuan-Ru , Li Hao-Ming , Kuo Hann-Chorng
Published: October 2022

(1) Background: Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) not only induces physiological damage but also greatly affects psychological stress. Multidisciplinary therapy has been recommended for IC/BPS treatment, but clinical trial data of combined bladder therapy and cognitive behavioral therapy (CBT) are lacking. This study evaluated CBT efficacy in patients with IC/BPS. (2) Methods: Patients with IC/BPS were randomized to the bladder monotherapy (BT) or combined CBT (CBT) group. The primary endpoint was the self-reported outcome by global response assessment (GRA). Secondary endpoints included IC symptoms and problem index, bladder pain score, Beck’s anxiety inventory (BAI), and depression inventory, and objective parameters were also compared. (3) Result: A total of 30 patients receiving BT and 30 receiving CBT therapy were enrolled. Significant improvement of the BAI at 8 (p = 0.045) and 12 weeks (p = 0.02) post-treatment was observed in the CBT group, with significantly greater GRA scores at 12 weeks (p < 0.001). Repeated measures analysis of variance showed a significant effect within the CBT group on IC/BPS patients’ self-reported treatment outcomes (p = 0.001) and anxiety severity BAI scores (p = 0.033). (4) Conclusion: A multimodal treatment of CBT combined with suitable bladder treatment more effectively improves anxiety severity and treatment outcomes in patients with IC/BPS.
The Role of Selected Serpins in Gastrointestinal (GI) Malignancies
Authors: Pączek Sara , Mroczko Barbara
Published: October 2022

Gastrointestinal (GI) cancers, which are a diverse group of malignant diseases, represent a major healthcare problem around the world. Due to the lack of specific symptoms in the early stages as well as insufficient diagnostic possibilities, these malignancies occupy the leading position in the causes of death worldwide. The currently available tests have too many limitations to be part of routine diagnostics. Therefore, new potential biomarkers that could be used as diagnostic and prognostic factors for these cancers are still being sought. Among the proteins that might fit this role are serpins, which are serine protease inhibitors. Although the serpins themselves have been known for many years, they have recently become the centre of attention for many authors, especially due to the fact that a number of proteins in this family are involved in many stages of neoplasia formation, from angiogenesis through tumour growth to progression. Therefore, the aim of this review is to present the current knowledge about the significance of serpins in GI malignancies, especially their involvement in the development and progression of oesophageal, gastric, pancreatic and colorectal cancers. This review summarises and confirms the important roles of selected serpins in the pathogenesis of various GI cancers and also points to their promising roles as therapeutic targets. However, due to the relatively nonspecific nature of serpins, future research should be carried out to elucidate the mechanisms involved in tumour pathogenesis in more detail.
Hidden Unstable Flap Should Be Suspected in Treating Intractable Pain from Medial Meniscus Horizontal Tear
Authors: Kim Young Mo , Joo Yong Bum , An Byung Kuk , Song Ju-Ho
Published: October 2022

(1) Background: The medial meniscus horizontal tear (MMHT) is known as a lesion that can be treated nonoperatively. However, some patients show persistent pain despite conservative treatments. In arthroscopic surgery for MMHT, surgeons often encounter unexpected unstable flaps, which can explain the intractable pain. This study aimed to determine whether preoperative factors could predict the hidden unstable flaps in MMHT. (2) Materials and Methods: Medical records of 65 patients who underwent arthroscopic partial meniscectomy (APM) for isolated MMHT during 2016–2020 were retrospectively reviewed. APM was indicated when there was no severe chondral degeneration and intractable localized knee pain in the medial compartment did not resolve despite conservative treatments. Unstable flap was confirmed based on arthroscopic images and operation notes. Each of the following preoperative factors were investigated using logistic regression analyses to determine whether they can predict an unstable flap: age, sex, body mass index, lower limb alignment, trauma history, mechanical symptoms, symptom duration, visual analogue scale (VAS), Lysholm score, cartilage wear of the medial compartment, and subchondral bone marrow lesion (BML). (3) Results: Hidden unstable flaps were noted in 45 (69.2%) patients. Based on univariate analyses for each preoperative factor, age, symptom duration, cartilage wear (of the femoral condyle and the tibial plateau), and subchondral BML were included in the multivariate logistic regression analysis. The results showed that symptom duration (p = 0.026, odds ratio = 0.99) and high-grade cartilage wear of the medial femoral condyle (p = 0.017, odds ratio = 0.06) were negatively associated with unstable flaps. A receiver operating characteristic curve was used to calculate the symptom duration at which the prediction of unstable flaps was maximized, and the cutoff point was 14.0 months. (4) Conclusions: More than two thirds of patients suffering intractable pain from MMHT had hidden unstable flaps. However, APM should not be considered when the symptom duration is more than 14 months or high-grade cartilage wear of the medial femoral condyle is noted.
Group-Based Trajectory Analysis for Postpartum Depression Symptoms among Chinese Primiparous Women
Authors: Xiong Juan , Fang Qiyu , Huang Lingling , Yan Xinyi , Zheng Xujuan
Published: October 2022

Background: Subgroups of individuals sharing similar patterns of postpartum depression (PPD) among Chinese women are unknown thus far. Using a group-based trajectory model, this study aimed to explore the subgroups of Chinese primiparous women that share similar patterns of PPD and to explore the predictors of PPD trajectory membership over the course of the first six months postpartum. Methods: In total, 674 first-time Chinese mothers were recruited, and their depression status was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at four time points. Findings: Around 18.0% of participants belonging to Group 1 labeled as “few or no symptoms” remained stable, with an EPDS score of less than 5 during a six-month postpartum period. Almost one-third of subjects fell within the second trajectory, labeled “subclinical but present symptoms”, and peaked into the range of mild PPD but mostly stayed in the minimal range and had few or no PPD symptoms. Group 3 included 31.2% of women labeled “minor PPD status”, and their mean EPDS scores increased to a peak of 14.66 at six weeks postpartum. Group 4, with “major PPD status”, comprised 19.2% of the population, and the mean EPDS scores dramatically increased, reaching a peak of 19.59 at 12 weeks postpartum. Fewer types of support and not attending parenting training were associated with membership in the minor and major PPD status trajectories. Conclusions: Almost half of the Chinese new mothers in the study were found to fall into the two groups with minor or major PPD status trajectories, who should be given more attention and awareness from health professionals and researchers. Understanding predictors of group membership could help health providers to identify folks to prioritize getting connected to care as well as forming targeted interventions. Less degree of received support and not attending parenting training were identified to predict PPD trajectory membership. The regular, routine screening of PPD should be conducted at least 12 weeks postpartum, especially for new mothers in the major PPD status trajectory.
Clinical Outcomes of Biodegradable versus Durable Polymer Drug Eluting Stents in Rotational Atherectomy: Results from ROCK Registry
Authors: Kim Kyung An , Her Sung-Ho , Lee Kyusup , Choi Ik Jun , Lee Jae-Hwan , Lee Jang Hoon , Lee Sang Rok , Lee Pil Hyung , Lee Seung-Whan , Yoo Ki Dong , Lee Su Nam , Jang Won Young , Moon Donggyu , Moon Keon-Woong , Yun Kyeong Ho , Lee Hyun-Jong
Published: October 2022

Background: The aim of this study was to compare the clinical outcomes of biodegradable polymer (BP) versus durable polymer (DP) drug eluting stents (DES) in patients with calcified coronary lesions who underwent rotational atherectomy (RA) and percutaneous coronary intervention (PCI). Methods: This study was based on a multicenter registry which enrolled patients with calcified coronary artery disease who received PCI using RA during between January 2010 and October 2019 from 9 tertiary centers in Korea. The primary outcome was 3-year all-cause mortality, and the secondary outcomes were cardiovascular death and target-lesion failure. Results: A total of 540 patients who underwent PCI using RA were enrolled with a follow-up period of median 16.1 months. From this registry, 272 patients with PCI using DP-DES and 238 patients with BP-SGDES were selected for analysis. PCI with BP-DES was associated with decreased all-cause mortality after propensity score matching (HR 0.414, CI 0.174–0.988) and multivariate Cox regression analysis (HR 0.458, HR 0.224–0.940). BP-DES was also associated with decreased cardiovascular mortality, but there was no difference in TLF between the two groups. Conclusions: BP-DES were associated with favorable outcomes compared to DP-DES in patients undergoing PCI using RA for calcified coronary lesions.
Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies
Authors: Banchi Marta , Fini Elisabetta , Crucitta Stefania , Bocci Guido
Published: October 2022

Metronomic chemotherapy (MC) is the frequent, regular administration of drug doses designed to maintain a low, but active, range of concentrations of chemotherapeutic drugs, during prolonged periods of time without inducing excessive toxicities. To date, more than 400,000 children and adolescents under the age of 20 are diagnosed with cancer, per year, with 80% survival in most high-income countries, but less than 30% in low- and middle-income ones. In this review, we summarized the principal preclinical and clinical studies involving the use of MC in the most common pediatric tumors, with an overview of efficacy, toxicity, pharmacokinetic profile, and biomarkers. The best advantages of MC are low toxicity, oral administration and, thus, the feasibility of a more comfortable, home-based treatment, therefore improving the quality of life of the children themselves and of their parents and caregivers. Moreover, MC could represent a valid method to reduce the economic burden of anticancer therapy in the pediatric setting.
Right Ventricle in Arterial Hypertension: Did We Forget Something?
Authors: Tadic Marijana , Cuspidi Cesare
Published: October 2022

Right ventricular remodeling has been neglected in patients with arterial hypertension as all studies have concentrated on the left ventricle and left atrial-ventricular and ventricular-arterial coupling. The development of novel imaging techniques has revealed significant impairment in the RV structure, systolic and diastolic function, and, afterwards, RV longitudinal mechanics. However, these changes are subclinical and can be detected only after comprehensive imaging analysis. The latest findings confirm the importance of RV hypertrophy, systolic, and diastolic dysfunction in the prediction of cardiovascular adverse events in the hypertensive population, representing an important clinical implication of these parameters. In clinical practice, 2D echocardiography is widely used for the evaluation of RV remodeling. However, existing techniques are largely underused and limited to a few basic parameters (RV thickness and TAPSE), which are not nearly enough for a detailed assessment of RV remodeling. In addition, 3D echocardiography provides the possibility of accurate evaluation of RV volumes and ejection fraction, which are comparable with results obtained by cardiac magnetic resonance (CMR)—a gold standard for the evaluation of the RV. The use of 3D echocardiography is limited due to its low availability, the lack of adequate software necessary for the calculation of results, and the necessity for a higher level of expertise. CMR provides all information required for a detailed assessment of RV structural, functional, and mechanical remodeling, and it is considered the reference method for this type of evaluation. Furthermore, it is the only technique that may provide tissue characterization and evaluation of the interstitial space, which is essential for hypertensive heart disease. The aim of this review is to provide the current level of evidence regarding RV remodeling in patients with arterial hypertension evaluated with different imaging techniques and various parameters from each method.
Digital Ischemia after Ultrasound-Guided Alcohol Injection for Morton’s Syndrome: Case Report and Review of the Literature
Authors: Biz Carlo , Bonvicini Barbara , Sciarretta Giovanni , Pendin Mattia , Cecchetto Giovanni , Ruggieri Pietro
Published: October 2022

The therapeutic algorithm for symptomatic Morton’s syndrome is not standardized as several managements have been proposed. Ultrasound-guided alcohol injection (USGAI) is one of the non-operative procedures described. This report presents the case of digital ischemia that occurred after alcoholization for the treatment of Morton’s syndrome. This complication is described for the first time in the scientific literature, and it should not only be added to the list of sequalae of USGAI, but more importantly, it should also be explained to the patient when this alternative treatment to traditional surgery is proposed.
Influence of Ceramic Particles Size and Ratio on Surface—Volume Features of the Naturally Derived HA-Reinforced Filaments for Biomedical Applications
Authors: Mocanu Aura-Cătălina , Miculescu Florin , Dascălu Cătălina-Andreea , Voicu Ștefan Ioan , Pandele Mădălina-Andreea , Ciocoiu Robert-Cătălin , Batalu Dan , Dondea Sorina , Mitran Valentina , Ciocan Lucian-Toma
Published: October 2022

The intersection of the bone tissue reconstruction and additive manufacturing fields promoted the advancement to a prerequisite and new feedstock resource for high-performance bone-like-scaffolds manufacturing. In this paper, the proposed strategy was directed toward the use of bovine-bone-derived hydroxyapatite (HA) for surface properties enhancement and mechanical features reinforcement of the poly(lactic acid) matrix for composite filaments extrusion. The involvement of completely naturally derived materials in the technological process was based on factors such as sustainability, low cost, and a facile and green synthesis route. After the HA isolation and extraction from bovine bones by thermal processing, milling, and sorting, two dependent parameters—the HA particles size (<40 μm, <100 μm, and >125 μm) and ratio (0–50% with increments of 10%)—were simultaneously modulated for the first time during the incorporation into the polymeric matrix. The resulting melt mixtures were divided for cast pellets and extruded filaments development. Based on the obtained samples, the study was further designed to examine several key features by complementary surface–volume characterization techniques. Hence, the scanning electron microscopy and micro-CT results for all specimens revealed a uniform and homogenous dispersion of HA particles and an adequate adhesion at the ceramic/polymer interface, without outline pores, sustained by the shape and surface features of the synthesized ceramic particles. Moreover, an enhanced wettability (contact angle in the ~70−21° range) and gradual mechanical takeover were indicated once the HA ratio increased, independent of the particles size, which confirmed the benefits and feasibility of evenly blending the natural ceramic/polymeric components. The results correlation led to the selection of optimal technological parameters for the synthesis of adequate composite filaments destined for future additive manufacturing and biomedical applications.
The Implementation of Laboratory Information Management System in Multi-Site Genetics Study in Africa: The Challenges and Up-Scaling Opportunities
Authors: Oluwole Oluwafemi Gabriel , Oosterwyk Chandre , Anderson Dominique , Adadey Samuel Mawuli , Mnika Khuthala , Manyisa Noluthando , Yalcouye Abdoulaye , Wonkam Edmond T. , Aboagye Elvis Twumasi , Dia Yacouba , Uwibambe Esther , Jonas Mario , Priestley Roy , Popel Kalinka , Manyashe Thumeka , de Cock Carmen , Nembaware Victoria , Wonkam Ambroise
Published: October 2022

This study describes the roles of laboratory information management systems (LIMS) in multi-site genetics studies in Africa. We used the HiGeneS Africa project as a case study. The study participants were recruited in six African countries between 2019 to 2021. The Baobab LIMS, a server–client-based system (an African-led innovation) was used for the coordination of the biospecimen. The development phase of the LIMS showcased the team formation, data collection, biospecimen collection, and shipment strategies. The implementation phase showcased the biospecimen registration, processing, and quality control (QC) analytics. The sample QC was done using Nanodrop, Qubit, and PicoGreen/gDNATapestation assays. The results showed that a total of 3144 study participants were recruited from Cameroon, Ghana, Mali, Rwanda, Senegal, and South Africa. The biospecimen registration provided a comprehensive registry that included patient demographics, genetic information, and clinical and blood/saliva samples from the proband and family relatives. The QC analyzes identified 30 samples that failed QC, linked to overdue storage in the freezer before DNA extraction. The LIMS components implemented in this project formed a structure that can be upscaled to artificial intelligence-based LIMS. In conclusion, this study represents the largest and the most diverse collection of biospecimens for the genetic study of hearing impairment in Africa to date. A well-characterized LIMS should be recommended for multi-site molecular studies, particularly in Africa, to enhance African participation in global genomic medicine.
Multi-Faceted Analysis of Airborne Noise Impact in the Port of Split (I)
Authors: Vukić Luka , Peronja Ivan , Glavinović Roko
Published: October 2022

This multi-faceted study deals with the analysis of the impact of noise emissions from the cargo terminals in the port of Split, especially in view of the proximity to inhabited areas and the growing number of registered issues and concerns due to its particular location. Three objectives are pursued: the identification of noise sources in the port area, an overview of strategic noise maps and simulations of noise propagation from ships at berth, and the calculation of external costs of noise pollution. In the first, preliminary part of the research project, by conducting a monitoring campaign and analyzing the data on strategic noise maps of the studied area, road and rail traffic were estimated as the main noise sources causing excessive noise emissions for all assessment periods: day (Lday), evening (Levening), night (Lnight), and day-evening-night (Lden) period. Industrial resources, including ports, were identified as having marginal noise emission levels. The calculation of the total external noise costs results in a damage value of €190,166/year, considering the number of affected inhabitants and the assumed noise levels. As an added value of the study, the simulation results of two scenarios have determined the noise propagation of a ship at berth and highlighted the zone of excessive noise under certain conditions. The results of this study should encourage the relevant institutions to strengthen noise management plans and introduce effective and continuous monitoring of noise emissions in critical areas.
Research on the Delimitation of Marine Spatial Pattern Based on the Goal of “Carbon Peaking and Carbon Neutrality”
Authors: Zhao Qiwei , Teng Xin , Zhang Panpan , Kang Wanchao , Meng Xue , Wang Shuang
Published: October 2022

In the context of carbon peaking and carbon neutrality (“double carbon”), it is urgent to clarify the effect of marine spatial planning (MSP) on carbon sink increases and emission reductions, since such planning acts as a spatial governance tool for the earth’s largest carbon pool. In this paper, a linkage model between marine spatial functional zones and carbon distribution is established. To explore the relationship between marine spatial functional zones and carbon, the study analyzed the carbon increase or reduction role of sea-use activities in each zone and considered the carbon sequestration function of the marine ecosystem itself. A marine spatial pattern of “Two Spaces and Four Carbon Areas” is proposed to present the linkage. A carbon distribution pattern in marine space is delimited using the linkage model and the current MSP in the case study of the city of Tangshan, Hebei, China. Some measures have been taken or planned to be taken in Tangshan to improve the carbon sink function of the ecosystem and the marine space. The supporting role of MSP in achieving the “double carbon” goal is studied, and the paths and suggestions for integrating the “double carbon” goal into MSP are explored.