bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study
Authors: Tawfeek Mohammed M. Mahdy , Ahmed Hanan Mohamed Abdel Hamid , Bor’i Ashraf , Rady Ahmed M. Nashaat Ali
Published: July 2023

Objective

The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK).

Patients and methods

This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT).

Results

Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes.

Conclusion and recommendation

PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.
Public perspectives on strays and companion animal management in Malaysia
Authors: Munir Syafiq Munir Ismail , Mokhtar Mohd Istajib , Arham Ahmad Firdhaus
Published: July 2023

Strays and companion animal management is a sensitive issue in Malaysia that incites solid and conflicting views. Through structured questionnaires administered to a random sample of 704 respondents, this study explored public opinion on a) causes of the stray animal population, b) the management of the stray animal population, and c) the national strategy on strays and companion Animal Management. The results show that 70.3% of respondents agreed that a lack of public awareness regarding animal care was the major contributor to the stray animal population. In addition, 58.1% of respondents felt that treating and vaccinating animals exposed to zoonotic diseases is a viable approach that could be instituted as a reasonable measure in stray animal population management. Finally, developing animal protection areas through a multi-stakeholder partnership strategy initiative recorded the highest support (48.4%) for intervention planning for stray animal management at a national level. Notably, a significant percentage of public responses were implicitly influenced by demographic variables. These findings provide valuable insights into public opinion regarding stray and companion animal management in Malaysia. These findings could inform the development of future legislation aimed at reducing the unfavorable effects of stray animal populations on humans and the ecology of Malaysia.
Effect of polydopamine and fluoride ion coating on dental enamel remineralization: an in vitro study
Authors: Choi Seok-Min , Jung Hee-Won , Ryu Ji Hyun , You Hyung-Keun
Published: July 2023

Background

Fluoride treatment is one of the most effective dental caries prevention methods. To continuously prevent dental caries, stably immobilizing the fluoride on the tooth enamel is highly desirable. This study aimed to evaluate the remineralization of tooth enamels by one-pot coating using polydopamine and fluoride ions.

Methods

To prepare the enamel specimens for polydopamine- and fluoride ion-coating, they were treated with polydopamine- and fluoride-containing gels. The enamel specimens were collected from human molars in a blind manner (n = 100) and were randomized into five treatment groups (n = 20, each): 1) untreated, 2) polydopamine-coated, 3) fluoride-containing gel-treated, 4) F varnish-treated, and 5) polydopamine- and fluoride ion-coated enamels. Vickers hardness number (VHN), morphology, and fluoride contents of the specimens were measured before and after the pH-cycling regimen.

Results

Polydopamine- and fluoride ion-coated enamels showed the highest fluoride content and lowest VHN reduction among the samples. The fluoride content of the polydopamine/fluoride ion (PD/F)-coated enamel was increased to 182 ± 6.6%, which was far higher than that of the uncoated enamel (112.3 ± 32.8%, P < 0.05). The changes in the VHN values (ΔVHN) of PD/F-coated enamel substrates showed a slight reduction in the VHN (-3.6%, P < 0.05), which was far lower than that in the control group (-18.9%, P < 0.05). In addition, scanning electron microscopy clearly supported the effect of polydopamine- and fluoride ion-coatings on the remineralization of enamel specimens.

Conclusion

Our findings suggest that one-pot treatments with polydopamine and fluoride ions could significantly enhance remineralization by inhibiting enamel demineralization through the prolonged retention of fluoride ions.
Massage protects skeletal muscle from injury during long-term heavy-duty exercise via integrin β1 and laminin 2 channels of basement membrane
Authors: Liu Qingsong , Jin Songlin , Li Lunyu , Ayi Liubu , Ding Haili
Published: July 2023

Background

Massage is widely used in exercise-induced skeletal muscle damage (EIMD). It has been proven that massage can improve the morphology and function of damaged skeletal muscle in multiple ways. However, whether massage can protect skeletal muscles from injury during long-term heavy-duty exercise has not yet been determined.

Methods

In this study, a rat model of overuse injury was established by eccentric running for 4 weeks, and pressing at constant pressure and frequency and massage were used as intervention methods to explore whether massage could protect skeletal muscle from injury through upregulating integrin and the basement membrane laminin.

Results

The results showed that compared with the model group, the ultrastructure of skeletal muscle in the massage group was relatively complete and clear, and the maximum isotonic and tetanic contraction forces were significantly increased (P < 0.01). In addition, in the massage group, β1 integrin expression was significantly increased, p-FAK protein expression was decreased, and the co-localization of β1 integrin and the basement membrane laminin 2 was significantly increased (P < 0.01).

Conclusion

Our study shows that during long-term heavy-duty exercise, massage can enhance the cell adhesion function mediated by integrin β1 and laminin 2 to protect skeletal muscle from injury and prevent the occurrence of overuse injury.
Patients’ rights in physicians’ practice during Covid-19 pandemic: a cross-sectional study in Romania
Authors: Plaiasu Maria Cristina , Alexandru Dragos Ovidiu , Nanu Codrut Andrei
Published: July 2023

Background

Although the Covid-19 epidemic challenged existing medical care norms and practices, it was no excuse for unlawful conduct. On the contrary, legal compliance proved essential in fighting the pandemic. Within the European legal framework for the pandemic, patients were still entitled to be treated equally, by a specialized physician, with the possibility of seeking a second medical opinion, in a confidential setting, following prior and informed consent. This study examines physicians’ practices regarding patients’ rights during the Covid-19 pandemic and the effects of age, experience, and specialty on physicians’ behavior and preferences. Additionally, it explores the nexus of malpractice complaints, malpractice fear, and legal compliance.

Methods

A cross-sectional study was conducted on a convenience sample of attending physicians and general practitioners to assess compliance with patients’ rights regulations. Respondents were physicians practicing in private and public settings in Southwestern Romania from July 2021 to May 2022.

Results

396 attending physicians and 109 general practitioners participated in the research. Attending physicians acknowledged patients’ rights in 55.7% of statements, while general practitioners showed a slightly higher level of compliance at 59.9%. Emergency and Anesthesia and Intensive Care physicians showed the lowest compliance. There were no significant behavioral differences based on physicians’ age, years in practice, work sector, or location. However, when faced with the question of prioritizing treatment for patients with similar medical conditions, 46.2% of attending physicians reported favoring the younger patients. This preference was common among physicians under 39. Additionally, over half of the attending physicians reported working outside their area of expertise due to staff shortages. Malpractice fear was high among physicians, although unrelated to patients’ claims, legal compliance, or working outside the scope of practice. It resulted in pressure and behavioral changes.

Conclusion

Adherence to patients’ rights was low during the Covid-19 pandemic. Physicians could benefit from educational and administrative support to ensure better legal compliance. Further research is needed to determine if this behavior persists beyond the pandemic context.
Global trans-lesional computed tomography-derived fractional flow reserve gradient is associated with clinical outcomes in diabetic patients with non-obstructive coronary artery disease
Authors: Liu Zinuan , Ding Yipu , Dou Guanhua , Wang Xi , Shan Dongkai , He Bai , Jing Jing , Li Tao , Chen Yundai , Yang Junjie
Published: July 2023

Background

Coronary computed tomography angiography (CCTA)-derived fractional flow reserve (CT-FFR) enables physiological assessment and risk stratification, which is of significance in diabetic patients with nonobstructive coronary artery disease (CAD). We aim to evaluate prognostic value of the global trans-lesional CT-FFR gradient (GΔCT-FFR), a novel metric, in patients with diabetes without flow-limiting stenosis.

Methods

Patients with diabetes suspected of having CAD were prospectively enrolled. GΔCT-FFR was calculated as the sum of trans-lesional CT-FFR gradient in all epicardial vessels greater than 2 mm. Patients were stratified into low-gradient without flow-limiting group (CT-FFR > 0.75 and GΔCT-FFR < 0.20), high-gradient without flow-limiting group (CT-FFR > 0.75 and GΔCT-FFR ≥ 0.20), and flow-limiting group (CT-FFR ≤ 0.75). Discriminant ability for major adverse cardiovascular events (MACE) prediction was compared among 4 models [model 1: Framingham risk score; model 2: model 1 + Leiden score; model 3: model 2 + high-risk plaques (HRP); model 4: model 3 + GΔCT-FFR] to determine incremental prognostic value of GΔCT-FFR.

Results

Of 1215 patients (60.1 ± 10.3 years, 53.7% male), 11.3% suffered from MACE after a median follow-up of 57.3 months. GΔCT-FFR (HR: 2.88, 95% CI 1.76–4.70, P < 0.001) remained independent risk factors of MACE in multivariable analysis. Compared with the low-gradient without flow-limiting group, the high-gradient without flow-limiting group (HR: 2.86, 95% CI 1.75–4.68, P < 0.001) was associated with higher risk of MACE. Among the 4 risk models, model 4, which included GΔCT-FFR, showed the highest C-statistics (C-statistics: 0.75, P = 0.002) as well as a significant net reclassification improvement (NRI) beyond model 3 (NRI: 0.605, P < 0.001).

Conclusions

In diabetic patients with non-obstructive CAD, GΔCT-FFR was associated with clinical outcomes at 5 year follow-up, which illuminates a novel and feasible approach to improved risk stratification for a global hemodynamic assessment of coronary artery in diabetic patients.
Hyaluronic acid-modified and verteporfin-loaded polylactic acid nanogels promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation
Authors: Chen Kun , Liu Yuanhu , Liu Xiaohui , Guo Yongli , Liu Jing , Ding Jiaojiao , Zhang Zheng , Ni Xin , Chen Yunsheng
Published: July 2023

Wound healing is a common occurrence. However, delayed healing and aberrant scarring result in pathological wound healing. Accordingly, a scarless wound healing remains a significant clinical challenge. In this study, we constructed hyaluronic acid (HA)-modified and verteporfin (VP)-loaded polylactic acid (PLA) nanogels (HA/VP-PLA) to promote scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Owing to the unique structure of HA incorporating and coating in VP-loaded PLA nanoparticles, HA/VP-PLA could be topically applied on wound to achieve targeted delivery to fibroblasts. Then, HA/VP-PLA released HA and lactic acid (LA) to stimulate the proliferation and migration of fibroblasts, as well as VP to inhibit Yes-associated protein (YAP) expression and nuclear localization to suppress fibrosis. In vitro (skin fibroblasts) and in vivo (rat and rabbit models) experiments strongly suggested that HA/VP-PLA promoted scarless wound healing by accelerating wound re-epithelialization and controlling scar formation. Therefore, our work provides a feasible strategy for scarless wound healing, and the sophisticated HA/VP-PLA exhibit a great potential for clinical applications.
Factors associated with alteration of nipple or skin sensation and impact of duration of time following nipple-sparing mastectomy (NSM): an analysis of 460 cases with comparison of conventional versus endoscopic- or robotic-assisted NSM
Authors: Lai Hung-Wen , Chang Yi-Lin , Chandrachamnong Korawan , See Mee-Hoong , Huang Hsin-I , Lin Shih-Lung , Fang Dar-Yuan , Chen Shou-Tung , Chen Dar-Ren , Mok Chi Wei , Cheng Fiona Tsui-Fen
Published: July 2023

Background

The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort.

Methods

Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database.

Results

A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The “time since surgery to last evaluation” was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ≦ 12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05).

Conclusion

Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer “time after surgery” was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches.

Synopsis

Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.
Age-related differences in eating location, food source location, and timing of snack intake among U.S. children 1–19 years
Authors: Tripicchio Gina L. , Croce Christina M. , Coffman Donna L. , Pettinato Cameron , Fisher Jennifer O.
Published: July 2023

Background

Snacking is nearly universal and contributes significant energy to U.S. children’s diets. Little is known, however, about where and when snacking intake occurs and if such patterns change with age. This research evaluated age-related differences in eating location, food source location, and timing of snacking among U.S. children aged 1–19 years (y).

Methods

A cross-sectional analysis of snacking among 14,666 children in the 2007–2018 U.S. National Health and Nutrition Examination Survey was conducted using a single 24-hour dietary recall. Snacking was participant-defined and included all eating occasions outside of meals. Linear regression and analysis of covariance were used to examine the effects of age (toddler 1–2 y, preschooler 3–5 y, school-age 6–11 y, adolescent 12–19 y) on the percentage of daily snack energy consumed by eating location (at home vs. away from home), food source location (grocery store, convenience store, school/childcare, restaurant, from someone else (i.e. “socially”), and other), and time of day (morning, 6am-12pm; early afternoon, 12pm-3pm; late afternoon/afterschool 3pm-6pm; evening 6pm-9pm, late-night 9pm-12am, and overnight 12am-6am).

Results

On average, U.S. children consumed most of their daily snacking energy at home (71%), from foods and beverages obtained from grocery stores (75%), and in the late afternoon/afterschool (31%). Toddlers and preschoolers consumed a greater percentage of their daily snack energy during the morning hours compared to school-age children and adolescents (both p < 0.001); school-age children consumed the most in the evening (27%, p < 0.001), and adolescents consumed the most in the late-night period (22%, p < 0.001). Age-related increases were seen in the percentage of daily snacking energy eaten outside the home (p < 0.001), and obtained socially (p < 0.001), from restaurants (p < 0.001), and convenience stores (p < 0.001).

Conclusion

Findings reveal age-related differences in eating location, food source location, and timing of snack intake among U.S. children aged 1–19 y. Younger children consume a greater percentage of snacking calories in the morning and at home relative to older children. School-age children and adolescents show greater snacking in the evening and at night and from foods obtained and eaten outside the home. Efforts to promote healthy snacking behaviors among children should consider developmental differences in snacking patterns.
A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC–OXPHOS axis
Authors: Jiang Ruibin , Chen Zhongjian , Ni Maowei , Li Xia , Ying Hangjie , Fen Jianguo , Wan Danying , Peng Chanjuan , Zhou Wei , Gu Linhui
Published: July 2023

Background

Ovarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), which enables cell growth, migration, and cancer stem cell maintenance, is a critical driver of disease progression and a potential intervention target of OC. However, the current OXPHOS intervention strategy mainly suppresses the activity of the electron transport chain directly and cannot effectively distinguish normal tissues from cancer tissues, resulting in serious side effects and limited efficacy.

Methods

We screened natural product libraries to investigate potential anti-OC drugs that target OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch assay, and xenograft model was applied to evaluate the anti-tumor mechanism of small molecules obtained by screening in OC.

Results

Gossypol acetic acid (GAA), a widely used gynecological medicine, was screened out from the drug library with the function of suppressing OXPHOS and OC progression by targeting the leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. GAA binds to LRPPRC directly and induces LRPPRC rapid degradation in a ubiquitin-independent manner. LRPPRC was overexpressed in OC, which is highly correlated with the poor outcomes of OC and could promote the malignant phenotype of OC cells in vitro and in vivo. GAA management inhibits cell growth, clonal formation, and cancer stem cell maintenance in vitro, and suppresses subcutaneous graft tumor growth in vivo.

Conclusions

Our study identified a therapeutic target and provided a corresponding inhibitor for OXPHOS-based OC therapy. GAA inhibits OC progression by suppressing OXPHOS complex synthesis via targeting LRPPRC protein, supporting its potential utility as a natural therapeutic agent for ovarian cancer.
Novel heavily fucosylated glycans as a promising therapeutic target in colorectal cancer
Authors: Tsai Kuei-Yen , Chang Yu-Jia , Huang Chien-Yu , Prince G. M. Shazzad Hossain , Chen Hsin-An , Makondi Precious Takondwa , Shen Ying-Rou , Wei Po-Li
Published: July 2023

Background

Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear.

Methods

This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model.

Results

Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth.

Conclusions

As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.
Mitochondrial dysfunction: roles in skeletal muscle atrophy
Authors: Chen Xin , Ji Yanan , Liu Ruiqi , Zhu Xucheng , Wang Kexin , Yang Xiaoming , Liu Boya , Gao Zihui , Huang Yan , Shen Yuntian , Liu Hua , Sun Hualin
Published: July 2023

Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.
Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress
Authors: Onda-Ohto Asako , Hasegawa-Ogawa Minami , Matsuno Hiromasa , Shiraishi Tomotaka , Bono Keiko , Hiraki Hiromi , Kanegae Yumi , Iguchi Yasuyuki , Okano Hirotaka James
Published: July 2023

Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology, induced the differentiation of these cells into motor and sensory neurons, and analyzed factors that are assumed to be altered in or associated with ALS (cell morphology, TDP-43 localization and aggregate formation, cell death, TDP-43 splicing function, etc.). We aimed to clarify the pathological alterations caused solely by TDP-43 mutation, i.e., the changes in human iPSC-derived neurons with TDP-43 mutation compared with those with the same genetic background except TDP-43 mutation. Oxidative stress induced by hydrogen peroxide administration caused the death of TDP-43 mutant-expressing motor neurons but not in sensory neurons, indicating the specific vulnerability of human iPSC-derived motor neurons with TDP-43 mutation to oxidative stress. In our model, we observed aggregate formation in a small fraction of TDP-43 mutant-expressing motor neurons, suggesting that aggregate formation seems to be related to ALS pathology but not the direct cause of cell death. This study provides basic knowledge for elucidating the pathogenesis of ALS and developing treatments for the disease.
Faecalibacterium prausnitzii alleviates inflammatory arthritis and regulates IL-17 production, short chain fatty acids, and the intestinal microbial flora in experimental mouse model for rheumatoid arthritis
Authors: Moon Jeonghyeon , Lee A. Ram , Kim Heejung , Jhun JooYeon , Lee Seon-Yeong , Choi Jeong Won , Jeong Yunju , Park Myeong Soo , Ji Geun Eog , Cho Mi-La , Park Sung-Hwan
Published: July 2023

Background

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that leads to joint destruction and functional disability due to the targeting of self-antigens present in the synovium, cartilage, and bone. RA is caused by a number of complex factors, including genetics, environment, dietary habits, and altered intestinal microbial flora. Microorganisms in the gut bind to nod-like receptors and Toll-like receptors to regulate the immune system and produce various metabolites, such as short-chain fatty acids (SCFAs) that interact directly with the host. Faecalibacterium prausnitzii is a representative bacterium that produces butyrate, a well-known immunomodulatory agent in the body, and this microbe exerts anti-inflammatory effects in autoimmune diseases.

Methods

In this study, F. prausnitzii was administered in a mouse model of RA, to investigate RA pathology and changes in the intestinal microbial flora. Using collagen-induced arthritic mice, which is a representative animal model of RA, we administered F. prausnitzii orally for 7 weeks.

Results

The arthritis score and joint tissue damage were decreased in the mice administered F. prausnitzii compared with the vehicle-treated group. In addition, administration of F. prausnitzii reduced the abundance of systemic immune cells that secrete the pro-inflammatory cytokine IL-17 and induced changes in SCFA concentrations and the intestinal microbial flora composition. It also resulted in decreased lactate and acetate concentrations, an increased butyrate concentration, and altered compositions of bacteria known to exacerbate or improve RA.

Conclusion

These results suggest that F. prausnitzii exerts a therapeutic effect on RA by regulation of IL-17 producing cells. In addition, F. prausnitzii modify the microbial flora composition and short chain fatty acids in experimental RA mouse model.
Bioactivities of Garcinia kola enzymatic hydrolysates at different enzyme–substrate ratios
Authors: Salami Salmat Adenike , Osukoya Olukemi Adetutu , Adewale Olusola Bolaji , Odekanyin Oludele , Obafemi Tajudeen Olabisi , Kuku Adenike
Published: July 2023

Natural products, such as enzymatic hydrolysates and bioactive peptides from dietary sources, are safe alternatives to synthetic compounds linked to various deleterious effects. The purpose of this study is to determine the in vitro bioactivities (antioxidant and anti-inflammatory activities) of Garcinia kola seeds enzymatic hydrolysates (GKPHs) at different enzyme (pepsin)-substrate ratios. G. kola protein, isolated by alkaline solubilization and acid precipitation, was hydrolyzed with pepsin at varying enzyme–substrate (E:S) ratios. The antioxidant parameters investigated include 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging, hydrogen peroxide scavenging and ferrous ion (Fe2+) chelating activities. For anti-inflammatory properties, membrane stabilization and protein denaturation activities tests were used. GKPH produced at 1:32 had the highest degree of hydrolysis (66.27 ± 4.21%). All GKPHs had excellent in vitro anti-inflammatory properties. However, only enzymatic hydrolysates produced at 1:16 (E:S) ratio chelated iron (II) and as well had the highest percentage hemolysis inhibition of 84.45 ± 0.007%, percentage protein denaturation inhibition of 53.36 ± 0.01% at maximum concentration and exhibited highest DPPH scavenging activity (87.24 ± 0.10%). The enzymatic hydrolysates had excellent solubility, emulsifying and foaming properties. It could be deduced from this study that pepsin at a ratio of 1:16 of G. kola protein produced the most effective enzymatic hydrolysates in terms of their antioxidant and anti-inflammatory activities. G. kola pepsin enzymatic hydrolysates, thus, have potential in development as functional foods and as therapeutics pharmaceutical industries in the management of diseases associated with oxidative stress and inflammation owing to their excellent functional, antioxidant and anti-inflammatory properties.
Potential of Y. lipolytica epoxide hydrolase for efficient production of enantiopure (R)-1,2-octanediol
Authors: Godase Vijaya P. , Kumar V. Ravi , Kumar Ameeta Ravi
Published: July 2023

The recombinant Yleh from a tropical marine yeast Yarrowia lipolytica NCIM 3589 exhibited a high epoxide hydrolase activity of 9.34 ± 1.80 µmol min-1 mg-1 protein towards 1,2-epoxyoctane (EO), at pH 8.0 and 30 °C. The reaction product was identified as 1,2-Octanediol (OD) by GC-MS using EO and H2O18 as substrate, affirming the functionality of Yleh as an epoxide hydrolase. For EO, the Km, Vmax, and kcat/Km values were 0.43 ± 0.017 mM, 0.042 ± 0.003 mM min-1, and 467.17 ± 39.43 mM-1 min-1, respectively. To optimize the reaction conditions for conversion of racemic EO by Yleh catalyst to enantiopure (R)-1,2-octanediol, initially, Response Surface Methodology was employed. Under optimized reaction conditions of 15 mM EO, 150 µg purified Yleh at 30 °C a maximal diol production of 7.11 mM was attained in a short span of 65 min with a yield of 47.4%. Green technology using deep eutectic solvents for the hydrophobic substrate (EO) were tested as co-solvents in Yleh catalyzed EO hydrolysis. Choline chloride-Glycerol, produced 9.08 mM OD with an increased OD yield of 60.5%. Thus, results showed that deep eutectic solvents could be a promising solvent for Yleh-catalyzed reactions making Yleh a potential biocatalyst for the biosynthesis of enantiopure synthons.
Predicting diagnostic biomarkers associated with immune infiltration in Crohn's disease based on machine learning and bioinformatics
Authors: Bao Wenhui , Wang Lin , Liu Xiaoxiao , Li Ming
Published: July 2023

Objective

The objective of this study is to investigate potential biomarkers of Crohn's disease (CD) and the pathological importance of infiltration of associated immune cells in disease development using machine learning.

Methods

Three publicly accessible CD gene expression profiles were obtained from the GEO database. Inflammatory tissue samples were selected and differentiated between colonic and ileal tissues. To determine the differentially expressed genes (DEGs) between CD and healthy controls, the larger sample size was merged as a training unit. The function of DEGs was comprehended through disease enrichment (DO) and gene set enrichment analysis (GSEA) on DEGs. Promising biomarkers were identified using the support vector machine-recursive feature elimination and lasso regression models. To further clarify the efficacy of potential biomarkers as diagnostic genes, the area under the ROC curve was observed in the validation group. Additionally, using the CIBERSORT approach, immune cell fractions from CD patients were examined and linked with potential biomarkers.

Results

Thirty-four DEGs were identified in colon tissue, of which 26 were up-regulated and 8 were down-regulated. In ileal tissues, 50 up-regulated and 50 down-regulated DEGs were observed. Disease enrichment of colon and ileal DEGs primarily focused on immunity, inflammatory bowel disease, and related pathways. CXCL1, S100A8, REG3A, and DEFA6 in colon tissue and LCN2 and NAT8 in ileum tissue demonstrated excellent diagnostic value and could be employed as CD gene biomarkers using machine learning methods in conjunction with external dataset validation. In comparison to controls, antigen processing and presentation, chemokine signaling pathway, cytokine–cytokine receptor interactions, and natural killer cell-mediated cytotoxicity were activated in colonic tissues. Cytokine–cytokine receptor interactions, NOD-like receptor signaling pathways, and toll-like receptor signaling pathways were activated in ileal tissues. NAT8 was found to be associated with CD8 T cells, while CXCL1, S100A8, REG3A, LCN2, and DEFA6 were associated with neutrophils, indicating that immune cell infiltration in CD is closely connected.

Conclusion

CXCL1, S100A8, REG3A, and DEFA6 in colonic tissue and LCN2 and NAT8 in ileal tissue can be employed as CD biomarkers. Additionally, immune cell infiltration is crucial for CD development.
Geolocation of a demersal fish (Pacific cod) in a high-latitude island chain (Aleutian Islands, Alaska)
Authors: Nielsen Julie K. , Bryan David R. , Rand Kimberly M. , Arostegui Martin C. , Braun Camrin D. , Galuardi Benjamin , McDermott Susanne F.
Published: July 2023

Background

Fish geolocation methods are most effective when they are customized to account for species behavior and study area characteristics. Here, we provide an example of customizing a hidden Markov model (HMM) for reconstructing movement pathways of a high-latitude demersal fish species in a remote island chain using Pop-up Satellite Archival Tag (PSAT) data. Adult Pacific cod were tagged with PSATs while occupying winter spawning grounds in the Aleutian Islands in February 2019. We adapted a demersal fish application of the HMM to (1) add light-based longitude to the data likelihood model, (2) account for possible off-bottom behavior of demersal fishes in the maximum daily depth likelihood, and (3) modify the model framework to accommodate convoluted island topography in the study area. A simulation study was conducted to explore the two primary modifications to the model framework, reflecting boundary for the movement kernel and the Viterbi method of pathway reconstruction, under known conditions.

Results

Geolocation was performed on satellite-transmitted and detailed archival data sets from 6 adult Pacific cod at liberty for 21–277 days. Migration from winter spawning to summer foraging areas (range 60–395 km) was detected for the 4 tagged fish that were at liberty for more than 90 days. Light-based longitude was the primary geolocation variable for detecting migrations with precision (root mean square error) estimates of 0.56 degrees during winter and 1.3 degrees during the summer. Simulation studies confirmed the effectiveness of model framework modifications and generated guidelines for use in specific applications.

Conclusions

This study demonstrates that post-spawning migrations of Pacific cod in the Aleutian Islands can be detected and characterized using PSAT data. Initial insights into migrations, summer foraging areas, and associated development of appropriate analysis tools will support future Pacific cod movement studies in the Aleutian Islands as well as other regions of Alaska. The adaptations to the HMM presented here will benefit current and future research on demersal fish in other regions as well as fish species that occupy areas with convoluted shorelines or island chain topography.
The identity of Fuegian and Patagonian “dogs” among indigenous peoples in southernmost South America
Authors: Jaksic Fabian M. , Castro Sergio A.
Published: July 2023

Background

By using a historical approach we attempt to answer the question of whether the “dogs” of Fuegian and Patagonian peoples are a domesticated dog (Canis lupus familiaris) or a tamed or domesticated Culpeo “fox” (Lycalopex culpaeus), or a cross breed.

Methods and results

We reviewed historical chronicles and current scientific papers, and clarified several rather confusing concepts, providing disambiguation for terms such as Magellanic region, Patagonia, and Tierra del Fuego; Fuegian and Patagonian peoples; and Fuegian and Patagonian dogs. We conclude that these dogs belong to two different canid varieties: The smaller domestic dog typical of the “canoe-indians” (Chonos, Kawesqar, and Yahgan peoples) and the larger tamed or domesticated Culpeo “fox" typical of the “foot indians” (Aonikenk, Manek'enk, and Selk’nam peoples, thus proposing the use of Fuegian and Patagonian dog, respectively.

Discussion

We think that the original Fuegian dog was indeed a Canis lupus familiaris brought along by the natives after the Bering’s crossing and that the Patagonian dog was a tame Culpeo fox Lycalopex culpaeus, which was progressively replaced by the more gregarious, human friendly, and colorful domestic dogs brought by European explorers, adventurers, colonizers, and settlers of Patagonia and Tierra del Fuego during the mid to late 1800s. The possibility that the Patagonian dog was a cross between domestic dog and Culpeo “fox” cannot be ruled out, but the only specimen genetically analyzed was closest to being the latter and not a hybrid.
Prediction of measles patients using machine learning classifiers: a comparative study
Authors: Gyebi Robert , Okyere Gabriel Asare , Nakua Emmanuel Kwaku , Aseidu-Bekoe Franklin , Nti Jane Serwaa Akoto , Ansah Emmanuel Owusu , Opoku Felix Agyemang
Published: July 2023

Background

Measles has high primary reproductive number, extremely infectious and ranked second to malaria in terms of disease burden in Ghana. Owing to the disease’s high infectious rate, making early diagnosis based on an accurate system can help limit the spread of the disease. Studies have been conducted to derive models to serve as preliminary tools for early detection. However, these derived models are based on traditional methods, which may be limited in terms of model sensitivity and prediction power. This study focuses on comparing the performance of five machine learning classification techniques with a traditional method for predicting measles patients in Ghana. The study was an analytical cross-sectional design of suspected measles cases in Ghana.

Results

The performance of six classifiers were compared and the random forest (RF) model demonstrated better performance among other models. The RF model achieved the highest sensitivity (0.88) specificity (0.96), ROC (0.92) and total accuracy (0.92).

Conclusions

Our findings showed that, despite all the six methods had good performance in classifying measles patients, the RF model outperformed all the other classifiers in terms of different criteria in prediction accuracy. Accordingly, this approach is an effective classifier for predicting measles in the early stage.
Survey of wastewater issues due to oil spills and pollution in the Niger Delta area of Nigeria: a secondary data analysis
Authors: Ewim Daniel Raphael Ejike , Orikpete Ochuko Felix , Scott Temiloluwa O. , Onyebuchi Chisom N. , Onukogu Amanda O. , Uzougbo Chinedum Gloria , Onunka Chiemela
Published: July 2023

Background

This paper presents a comprehensive analysis of the issue of wastewater due to oil spills and pollution in the Niger Delta region of Nigeria, which has led to significant environmental and socioeconomic consequences for local communities. The study employed a secondary data collection approach, drawing on various sources, including published research articles, reports, official records, and satellite imagery.

Main body of the abstract

Through a systematic review and synthesis of the available literature, the paper identified key challenges, mitigation and remediation strategies, policy recommendations, and areas for future research. The findings of this study revealed that the existing regulatory framework has not been fully effective in preventing and addressing oil spills and pollution in the Niger Delta region due to factors such as weak enforcement, inadequate resources, and overlapping responsibilities among regulatory agencies. Moreover, existing measures for oil spill response, clean-up, compensation, and remediation have had limited success, leaving affected communities to continue suffering from the impacts of oil spills and pollution.

Short conclusion

The paper highlights the potential of innovative approaches and technologies, such as advanced oil spill detection and monitoring technologies, bioremediation, and renewable energy, to enhance the effectiveness of mitigation and remediation efforts. Furthermore, the study emphasizes the importance of collaboration and cooperation among various stakeholders, including government agencies, oil companies, local communities, civil society organizations, and international partners, in addressing the challenges posed by oil spills and pollution in the Niger Delta region. Based on the findings, the paper presents several policy recommendations, such as strengthening the regulatory framework, enhancing transparency and accountability, promoting community participation and empowerment, and encouraging investment in sustainable development and clean technologies.
Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort
Authors: Bonfiglioli Karina Rossi , de Medeiros Ribeiro Ana Cristina , Carnieletto Ana Paula , Pereira Ivânio , Domiciano Diogo Souza , da Silva Henrique Carriço , Pugliesi Alisson , Pereira Leticia Rocha , Guimarães Maria Fernanda Resende , Giorgi Rina Dalva Neubarth , Reis Ana Paula Monteiro Gomides , Brenol Claiton Viegas , Louzada-Júnior Paulo , da Cunha Sauma Maria de Fátima Lobato , Radominski Sebastião Cezar , da Mota Licia Maria Henrique , da Rocha Castelar-Pinheiro Geraldo
Published: July 2023

Introduction

Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients.

Objective

To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables.

Method

Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann–Whitney U-test, and Fisher’s exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05).

Results

1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) (‘p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group.

Conclusions

ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.
Development from recurrent anti-N-methyl-D-aspartate receptor encephalitis with seizures as the first symptom to autoimmune-associated epilepsy: a case report
Authors: Qin Ningxiang , Wang Jing , Peng Xi , Wang Liang
Published: July 2023

Background

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a novel autoimmune encephalitis (AE) first identified in 2007. It provides a new direction for clinicians when encountering unexplained symptoms such as seizures, psychotic behavioral abnormalities, speech disorders, and involuntary movements. Most patients have a good prognosis after immunotherapy, but some may experience relapses.

Case presentation

We report a Chinese female patient diagnosed with anti-NMDAR encephalitis. Over the past 30 years, the patient had experienced eight episodes with seizures as the first symptom, which eventually progressed to autoimmune-associated epilepsy. In the last two episodes, both serum and cerebrospinal fluid of the patient were negative for AE-related antibodies, and brain magnetic resonance imaging (MRI) revealed abnormal hyperintensity in the bilateral hippocampi. The patient's symptoms were poorly controlled by immunotherapy but well controlled by anti-seizure medicines.

Conclusions

Patients with a long history of AE and multiple relapses that start with seizures may display alterations of brain structure. Physicians should pay attention to autoimmune-associated epilepsy.