bluuebunny/crossref_metadata_2025 huggingface dataset:
RBP4 promotes denervation‐induced muscle atrophy through STRA6‐dependent pathway
Authors: Zhang Kang‐Zhen , Li Jia‐Wen , Xu Jin‐Shui , Shen Zheng‐Kai , Lin Yu‐Shuang , Zhao Can , Lu Xiang , Rui Yun‐Feng , Gao Wei
Published: June 2024

Backgrounds

Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear.

Methods

Denervation‐induced muscle atrophy model was constructed in wild‐type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol‐free RBP4 (apo‐RBP4), retinol‐bound RBP4 (holo‐RBP4) or oral gavage of RBP4 inhibitor A1120. Holo‐RBP4‐stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross‐sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed.

Results

The expression levels of RBP4 in skeletal muscles were significantly up‐regulated more than 2‐fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation‐induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin‐1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol‐bound holo‐RBP4 aggregated denervation‐induced ectopic fat accumulation and muscle atrophy. Consistently, holo‐RBP4 stimulation also had a dose‐dependent effect on the reduction of C2C12 myotube diameter and myofibre cross‐sectional area, as well as on the increase of Atrogin‐1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo‐RBP4 treatment increased the expression of its membrane receptor STRA6 (>3‐fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin‐1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3‐fold) in holo‐RBP4‐treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation‐induced muscle atrophy (30% increased myofibre cross‐sectional area) in mice.

Conclusions

In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6‐dependent and JAK2/STAT3 pathway‐mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.
Identification of clinical‐biological features of newly diagnosed early relapse multiple myeloma patients eligible for autologous stem cell transplantation
Authors: Cillo Lorenzo , Palma Anna Benedetta Dalla , Ricci Stefania , Pedrazzoni Mario , Scita Matteo , Bernardi Matia , Sammarelli Gabriella , Pelagatti Laura , Giuliani Nicola
Published: June 2024

A portion of multiple myeloma (MM) patients relapse early or do not respond to first line treatment. Identification of possible clinical and or biological features of these patients remains an unmet medical need. In this study we assesed the predictive markers for early relapse MM, defined as a progressive disease that occurred within 18 months, from autologoust stem cell transplantation (ASCT) in MM patients who did not have primary refractory disease. 74 consecutive MM patients were included in the study that received intensive therapy with ASCT. The study was able to identify the main features of newly diagnosed ER MM patients eligible for ASCT identifying the IgA isotype and the R2‐ISS score system as the main predictive prognostic factors for ER in this cohort of MM patients.
Desmopressin for prevention of bleeding for thrombocytopenic, critically ill patients undergoing invasive procedures: A randomised, double‐blind, placebo‐controlled feasibility trial
Authors: Desborough Michael J. R. , Laing Emma , Kounali Daphne , Mora Ana , Hodge Renate , Martin Siobhan , Thomas Helen , Hudson Cara , Parsons Joseph , Shah Akshay , Hutton Paula , Parke Tim , Wise Matthew P. , Morgan Matthew , McKechnie Stuart , Stanworth Simon J.
Published: June 2024

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 109/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty‐three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post‐procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures.
Gastrectomies for the treatment of gastric cancer in a reference cancer center present better pathological results and survival compared to non‐specialized hospitals
Authors: Ramos Marcus F. K. P. , Pereira Marina A. , Santos Sarah Moreira , Dias Andre R. , Ribeiro‐Junior Ulysses
Published: June 2024

Background

Some studies have shown that gastrectomy performed by experienced surgeons in high‐volume specialized hospitals with the possibility of complete treatment has better results. This study aimed to compare the results of patients who underwent surgery at a reference center with non‐specialized centers.

Methods

Patients with gastric adenocarcinoma stage as pTNM II and III who underwent curative gastrectomy and were referred for adjuvant chemotherapy between 2009 and 2018 were included. Patients were divided into two groups: patients operated on in a reference center with complete oncological treatment (Reference Group); and those operated on in an external Hospital and referred for adjuvant treatment at the reference center (External Group).

Results

A total of 643 patients were evaluated, 307 in the external group and 336 in the reference group. Patients in the external group were younger (58.9 vs. 62.6 years; p < 0.001) and with fewer comorbidities according to the Charlson‐Deyo index (p < 0.001). The pathological result showed more dissected lymph nodes (41.4 vs. 23.5; p < 0.001) and a higher R0 resection rate (98.5% vs. 95.1%; p = 0.013) in the reference group. Patients of the external group underwent more adjuvant radiotherapy (49.5% vs. 33.9%; p < 0.001) with no difference concerning adjuvant chemotherapy (p = 0.066). Peritoneal recurrence was more common in the external group (63.2% vs 38.7%, p < 0.001). The disease‐free survival rate was higher in the reference group (p < 0.001) as well as overall survival (p = 0.01).

Conclusion

Patients who received full oncological treatment at a reference center had better survival outcomes compared to those operated in external services.
Separation and purification of benzylester glucosides and derivatives from tubers of Gymnadenia conopsea (L.) R. Br. by linear gradient counter‐current chromatography combined with elution‐extrusion mode
Authors: Feng Qixiang , Zhang Zhe , Sun Mingze , Wang Zheng , Xu Xiaohui , Chen Qixu , Cheng Yuxing , Yin Zhuoyue , Dong Haoyu , Feng Yu , Wang Daijie
Published: June 2024

Tubers of Gymnadenia conopsea (L.) R. Br. (Orchidaceae), a traditional medicine and food homologous plant, has a broad application and development prospect in the food and drug industries. Benzylester glucosides, the main effective active components in this plant, are difficult to separate due to their similar structures and high polarity. In this study, linear gradient counter‐current chromatography was used to separate benzylester glucosides and derivatives, combined with elution‐extrusion mode. The main separation parameters were optimized, including the ratio of mobile phase and sample loading. Finally, seven compounds were successfully separated, including 4‐hydroxybenzyl alcohol (1), 4‐hydroxybenzaldehyde (2), dactylorhin B (3), loroglossin (4), dactylorhin A (5), 4‐(ethoxymethyl) phenol (6), and militarine (7). The structures were analyzed by mass spectrometry and nuclear magnetic resonance spectrometry. According to our findings, the established method was an efficient approach to separate benzylester glucosides and derivatives from tubers of G. conopsea. The established strategy could be applied to purify other similar high‐polarity compounds from complex natural products.
A robust ultra‐performance liquid chromatography‐tandem mass spectrometry method for simultaneous determination of 10 components in glutathione cycle
Authors: Qin Xiang‐Ling , Wang Si‐Yu , Li Qi‐Long , Wang Jun‐Jie , Yao Zhong‐Wei , Zhu Jin‐Hao , Chen Lin‐Xia , Huo Jie‐Ge , Li Song‐Lin , Zhou Jing , Zhu He
Published: June 2024

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra‐performance liquid chromatography‐tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ‐glutamylcysteine; cysteinyl‐glycine; n‐acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ‐glutamylcysteine, cysteinyl‐glycine, n‐acetylcysteine, cysteine, and homocysteine were derivatized by n‐ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from ‐3.42 to 10.92), stability (RSD% < 5.68, RE% range from ‐2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.
Comparing Outcomes Between Standard Mepilex and Mepilex Silver for Tracheotomy Dressings
Authors: Marcet‐Gonzalez Jessie , Mizu Ruth K. , Brown Jennifer N. , Prasla Heena N. , Pham Tien , Ongkasuwan Julina , Lambert Elton , Raynor Tiffany , Bedwell Joshua R.
Published: June 2024

Objective

The purpose of the study is to compare the incidence of early postoperative tracheotomy stoma wound complications in pediatric patients using a silver‐impregnated barrier dressing (Mepilex Ag) versus a standard absorbent foam dressing (standard Mepilex).

Methods

This is a prospective, non‐blinded, randomized trial of pediatric patients undergoing tracheotomy at a tertiary care children's hospital. Patients were randomized to receive Mepilex Ag versus standard Mepilex tracheostoma dressings following tracheotomy. All patients received standard postoperative wound care and daily stomal examination. Wound related complications, breakdown, granulation, and infection were recorded for the first 7 days after surgery. A non‐inferiority study design was used to test the hypothesis that the Mepilex group had a non‐inferior wound complication rate (within 10% margin) compared to the Mepilex Ag group.

Results

Eighty‐two patients were enrolled; 52 received Mepilex Ag, and 30 received standard Mepilex. There was no difference between the groups with respect to age, sex, race, surgical indication, or postoperative length of stay. Non‐inferiority testing demonstrated that the Mepilex standard cohort had no more than 10% greater stomal wound complication rate than that of Mepilex Ag dressing group (p = 0.0108).

Conclusion

Standard Mepilex was found to be non‐inferior to Mepilex Ag in the prevention of tracheotomy stomal wound complications. Standard Mepilex may be used effectively in the postoperative period, potentially reducing costs to caregivers and the institution. Further work is needed to analyze additional factors that could contribute to poor postoperative stoma healing such as bacterial colonization.

Level of Evidence

Randomized Controlled Trial, 2 Laryngoscope, 134:5160–5163, 2024
Association of Hearing Loss Onset and Etiology with Psychosocial Outcomes Among US Older Adults
Authors: Gallagher Tyler J. , Jamal Malaika , Choi Janet S.
Published: June 2024

Objective

Understand the differential association of onset and etiology of hearing loss with psychosocial outcomes among older adults.

Methods

This is a cross‐sectional cohort study based on 2017–2020 National Health and Nutrition Examination Survey. Adults aged ≥70 years who completed audiometric testing and questionnaires on onset and etiologies of hearing loss were included (n = 612). Outcomes included report of social avoidance and major depressive disorder (MDD, PHQ‐9). Multivariable regression was utilized to examine differential associations of onset and etiology of hearing loss on psychosocial outcomes while adjusting for relevant factors.

Results

In this nationally representative sample of US older adults with hearing loss, 20.8% [95%CI: 14.5–29.0%] reported social avoidance due to hearing loss and 7.2% [95%CI: 4.3–11.8] reported symptoms suggestive of MDD. Multivariable regression demonstrated self‐reported onset of hearing loss between ages 6–19 years (OR:2.49 [95%CI: 1.52–4.10]) and 20–59 years (OR:1.95 [95%CI: 1.07–3.55]) was associated with higher avoidance of social interaction than reported onset at ≥70 years. Those with onset between 20–59 years (OR:4.28 [95%CI: 1.17–15.6]) and 60–69 years (OR:5.68 [95%CI: 1.85–17.5]) were more likely to report symptoms consistent with MDD than those with onset at ≥70. Multivariable regression did not demonstrate increased risk of avoiding social interactions or MDD due to hearing loss from noise exposure, ear infection, or ear disease versus aging alone.

Conclusion

There was an association between earlier hearing loss onset with social avoidance and MDD. This suggests a need for research to investigate the impact of earlier diagnosis and intervention for hearing loss on psychosocial outcomes.

Level of Evidence

2b Laryngoscope, 134:5073–5079, 2024
Study of phosphorus status and sorption properties in reclaimed lignite mine soils under different age stands of Robinia pseudoacacia L. in Welzow, Germany
Authors: Hashar Mohammad Rafiul , Nasrin Shamima , Freese Dirk , Veste Maik
Published: June 2024

Due to the open‐cast mining activities, a large area in the Lusatian region in eastern Germany was left unproductive. Robinia pseudoacacia L. was planted within different ages in that large area as a short rotation coppice for woody biomass cultivation as well as to increase soil nutrients by increasing plant phosphorous (P) availability, accumulating organic matter input and biological nitrogen fixation. In this experiment, soil chemical analysis has been done to investigate the improvement and status of P in the mining soil depending on the ages of plantation (16, 17, 18, and 27 years old) of Robinia pseudoacacia L. The results show a higher P sorption in the oldest site, and the average P sorption capacity (PSC) obtained in the oldest site was 21.0 mmol Kg−1, which was 3–4 times higher than the youngest site. However, all the values were very low compared with the optimum plant growth level, and low P desorption indicates a low level of plant‐available P in the soil. The lower sorption properties with the small amount of oxalate iron (Feox) and oxalate aluminum (Alox) indicate the general P deficiency in the soil. However, a comparison from a previous study on the same experimental areas shows that not much improvement has occurred in soil P, and the change in soil P dynamics is very low. Nevertheless, the improvement of the values with increasing ages of Robinia pseudoacacia L. indicates that further improvement may be expected in soil nutrients with time.
Luminescence Improvement of Hybrid Zinc‐Based Halides via Sb3+‐Doping for Flexible X‐Ray Imaging
Authors: Liang Dehai , Wang Meng , Zhao Shuangyi , Xu Zhiyuan , Qaid Saif M. H. , Qian Qingkai , Zang Zhigang
Published: June 2024

Recently, zinc‐based metal halides have attracted numerous attention due to their excellent stability, low toxicity, and wide bandgaps. However, [ZnX4]2− tetrahedra in zinc‐based halides are found to be non‐optically active, which leads to poor photoluminescence quantum yields (PLQYs). Herein, Sb3+ ions are doped into hybrid zinc‐based halides of (C8H26N4)ZnCl6 single crystals (SCs) via an evaporative crystallization method. Compared with undoped (C8H26N4)ZnCl6 SCs with weak blue emission, Sb3+‐doped (C8H26N4)ZnCl6 SCs exhibit a strong broadband emission centered at 694 nm with a high PLQY of 67%, which is confirmed to be derived from self‐trapped excitons (STEs) of Sb3+ luminescent centers. Subsequently, Sb3+‐doped (C8H26N4)ZnCl6 is employed in flexible scintillation films, which demonstrates remarkable X‐ray imaging of complex objects with a spatial resolution of 3.6 lp mm−1 and a detection limit of 123.8 µGyair s−1, proving its promising potential in flexible X‐ray imaging applications.
All‐Biomass‐Based Hierarchical Photonic Crystals with Multimode Modulable Structural Colors and Morphing Properties for Optical Encryption
Authors: Ji Yue‐E , Wang Yushu , Wang Ziting , Wang Tao , Fu Yinghao , Zhu Zhenghua , Wang Yu , Ma Lingling , Lu Yanqing
Published: June 2024

Materials with structural coloration capable of multimode color manipulation are gaining growing significance for advanced encryption and high‐security anti‐counterfeiting applications. Among the most promising candidates are naturally derived biomaterials, owing to their renewable, biocompatible, and biodegradable features for developing sustainable, bio‐interfaced photonic platforms. Nevertheless, structural color encryption strategies developed from biological materials usually exhibit limited optical operation modes, lowering their encryption capability and security level. Here, an all‐biomass‐based photonic crystal platform is reported that hierarchically integrates chiral nematic and inverse opal structures through a combination of colloidal assembly, silk protein self‐assembly, and chiral self‐assembly of cellulose nanocrystals, enabling multiplex structural color manipulation in 2D and 3D spaces. The platform's Janus‐style integration brings specular and diffuse reflection, direction‐dependent reflection, circular dichroism, and birefringence into a single form, thereby facilitating multimode structural color tuning in a 2D plane by altering the illumination‐viewing modes. The inherent shape plasticity of silk proteins allows the subsequent creation of 3D photonic platforms with diverse configurations, offering additional spatial flexibility for color encoding. It is demonstrated that this all‐biomass‐based photonic framework exhibits versatile, multilevel, and high‐capacity encryption capability in 2D and 3D spaces, representing an innovative solution to bolster security measures against counterfeiting for future technologies.
Application of Organic Gel on Skin Realized by Hydrogel/Organic Gel Adhesion
Authors: Hu Ziqing , Tang Wei , Ji Xiaofan
Published: June 2024

Diversity in solvent selection bestows the organic gel with appealing characteristics embracing antidrying, anti‐icing, and antifouling abilities. However, organic gel, subjected to the “toxic” inherent property of solvent, is not able to be manipulated on skin. Herein, introducing the hydrogel layer amid organic gel and skin is envisaged to realize application of organic gel on skin. Hydrogel, inserted as the medium layer, works for the coupling role between skin and organic gel, also avoids the direct contact of organic gel toward skin. First, hydrogel system composed of acrylic acid is fabricated, meanwhile organic gel is prepared employing 2‐hydroxyethyl methacrylate, ethylene glycol (EG) as solvent. Organic gel is able to adhere to hydrogel by hydrogen bonding resulting from carboxyl groups of polyacrylic acid chains and hydroxyl groups occurring on 2‐hydroxyethyl methacrylate or EG. Additionally, hydrogen bonding enables the hydrogel to be firmly attached to skin, thus organic gel/hydrogel/skin assembly is produced. The further application of organic gel is exploited by incorporating stimuli‐responsive dyes including spiropyran and rhodamine derivative.
Adaptive light intensity aided wavelength tuning for phase‐shifting interferometric measurement system
Authors: Lu Qingjie , Wang Ji , Liu Wenjing , Liu Chang
Published: June 2024

In phase‐shifting interferometric measurement system, using wavelength‐tuned phase‐shifting technology to measure optical surface can improve vibration errors. However, the wavelength‐tuned phase‐shifting interferometry is greatly challenged by nonlinear distortion between wavelength‐tuned light intensity and voltage modulation, which has a certain impact on phase calculation accuracy. To address this issue, an adaptive light intensity‐aided interferometric measurement scheme is proposed in this study. To improve the adjustment time of voltage response, an improved fuzzy single‐neuron adaptive proportional differential integral constant amplitude control algorithm is built. By exploiting the online detection and feedback control of light intensity, the stable output of light intensity is integrated into phase‐shifting measurement system. Experiment results verify that the improvement of light intensity fluctuation range, root mean square, and peak‐to‐valley measurement repeatability can be achieved with the proposed scheme.
Clinical and patient‐reported outcomes and neurofilament response during tofersen treatment in SOD1‐related ALS—A multicenter observational study over 18 months
Authors: Meyer Thomas , Schumann Peggy , Weydt Patrick , Petri Susanne , Weishaupt Jochen H. , Weyen Ute , Koch Jan C. , Günther René , Regensburger Martin , Boentert Matthias , Wiesenfarth Maximilian , Koc Yasemin , Kolzarek Felix , Kettemann Dagmar , Norden Jenny , Bernsen Sarah , Elmas Zeynep , Conrad Julian , Valkadinov Ivan , Vidovic Maximilian , Dorst Johannes , Ludolph Albert C. , Hesebeck‐Brinckmann Jasper , Spittel Susanne , Münch Christoph , Maier André , Körtvélyessy Péter
Published: June 2024

Introduction/Aims

In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1‐ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient‐reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany.

Methods

Sixteen SOD1‐ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS‐PR), as measured by the monthly change of the ALS functional rating scale—revised (ALSFRS‐R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM‐9), and Net Promoter Score (NPS).

Results

Mean tofersen treatment was 11 months (6–18 months). ALS‐PR showed a mean change of −0.2 (range 0 to −1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS‐R. SVC was stable (mean 88%, range −15% to +28%). sNfL decreased in all patients except one heterozygous D91A‐SOD1 mutation carrier (mean change of sNfL −58%, range −91 to +27%, p < .01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM‐9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80).

Discussion

Data from this EAP supported the clinical and sNfL response to tofersen in SOD1‐ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.
How to promote geophysics as a standard tool for geotechnical investigations
Authors: Gustafsson J. , Higgs H.
Published: June 2024

There are a number of success stories of how geophysical investigations have been combined with geotechnical investigations to increase the knowledge of our subsurface from around the world. However, there is still a lack of understanding between these two professions, geophysicists and geotechnical engineers. The lack of understanding mainly considers what different geophysical methods deliver in form of results and accuracy. To promote the use of geophysical investigations even more, we need to address the purpose and expectations of the geophysical investigations, the awareness of method limitations and uncertainties of the different methods, and which standards and tools for interpretation and visualization are used.
A Scoping Review of Pain Management After Transoral Robotic Surgery
Authors: Snyder Vusala , Kraft Daniel O. , Creamer Andrew , Spector Matthew E. , Sridharan Shaum S.
Published: June 2024

Objective

Pain following transoral robotic surgery (TORS) is a driver of adverse outcomes and can lead to readmission and treatment delays. A scoping review was conducted to characterize TORS‐related pain and identify key management strategies utilized in the literature.

Data Sources

OVID Medline, CINAHL, Cochrane, Pubmed, and Embase databases were queried.

Review Methods

Two team members independently screened titles and abstracts and completed full‐text reviews. Studies examining TORS for OPSCC with quantitative pain data were included. The study followed the PRISMA guidelines.

Results

A total of 1467 studies were imported for screening and 25 studies were ultimately included. The average study sample size was 89 participants. 68% were conducted in a single‐center academic setting. Pain was assessed on varying timelines up to 3 years using 13 different metrics. Pain peaks days‐weeks postoperatively and returns to baseline thereafter. Postoperative pain is a significant cause of morbidity and limited data exist about optimal management.

Conclusion

Prospective studies are needed to characterize and address TORS‐related pain.
Reflexive thematic analysis of interviews with postprimary educators' experience and attitudes toward concussion
Authors: Conaghan Caomhan , Daly Ed , Ryan Lisa
Published: June 2024

Concussions from sport and recreational activities can negatively impact academic performance in adolescents. This study aims to use reflexive thematic analysis to understand the knowledge, management, and education of concussion among Irish postprimary educators. A cross‐sectional study that involved semistructured interviews with 18 secondary school teachers was conducted. Interviews were recorded and transcribed in preparation for a reflexive thematic analysis process according to research conducted by Braun and Clarke. A total of 664 data items were coded which led to the development of 5 themes (i.e., teacher's background experience, consequences of concussion, concussion in school, educating educators, and existing standards) and 22 subthemes. The implementation of concussion education initiatives for improving student safety, injury management, and recovery through mandatory teacher‐continued professional development should be explored. Teachers' knowledge of concussion is influenced by personal experiences, with safer attitudes observed in those who have witnessed or experienced concussions. The role of the Year Head in concussion management should be explored with a focus on communication pathways and dissemination of materials. Protocols for medical emergencies and academic adjustments for concussed students should be made readily available to secondary school teachers.
Decision‐making regarding safety investments: A case study of fluidized‐bed reactors
Authors: Sano Kazuhiko , Koshiba Yusuke
Published: June 2024

In chemical plants, the pressure to prioritize production and minimize operating costs often leads to delays in safety investments. To allocate limited management resources effectively, decision‐making regarding safety investments must follow a logical approach. This article outlines how engineers can provide valuable information to the management, enabling them to make informed decisions. We demonstrate that decision‐making involves both technical and economic considerations, following a well‐defined process with distinct stages. This study highlights the importance of technical data in making informed decisions regarding safety investments. Decision makers must consider various factors, including risk assessment, economic efficiency, technology reliability, and construction safety. In addition, economic efficiency considerations should incorporate new proposals that account for environmental profit/loss. Our findings confirm that effectiveness of the proposed method, particularly when applied to fluidized‐bed reactors. In conclusion, accurate allocation of management resources at appropriate times leads to reasonable risk reduction.
Infectious viruses and neurodegenerative diseases: The mitochondrial defect hypothesis
Authors: Jiang Tianshi , Zhu Kaili , Kang Guangli , Wu Guojun , Wang Lili , Tan Yurong
Published: June 2024

Global attention is riveted on neurodegenerative diseases due to their unresolved aetiologies and lack of efficacious therapies. Two key factors implicated include mitochondrial impairment and microglial ageing. Several viral infections, including Herpes simplex virus‐1 (HSV‐1), human immunodeficiency virus (HIV) and Epstein‐Barr virus, are linked to heightened risk of these disorders. Surprisingly, numerous studies indicate viruses induce these aforementioned precipitating events. Epstein‐Barr virus, Hepatitis C Virus, HIV, respiratory syncytial virus, HSV‐1, Japanese Encephalitis Virus, Zika virus and Enterovirus 71 specifically impact mitochondrial function, leading to mitochondrial malfunction. These vital organelles govern various cell activities and, under specific circumstances, trigger microglial ageing. This article explores the role of viral infections in elucidating the pathogenesis of neurodegenerative ailments. Various viruses instigate microglial ageing via mitochondrial destruction, causing senescent microglia to exhibit activated behaviour, thereby inducing neuroinflammation and contributing to neurodegeneration.
Astrovirus induced nonpurulent encephalomyelitis in sheep: First report from Türkiye by high‐throughput sequencing
Authors: Eroksuz Yesari , Timurkan Mehmet Ozkan , Shams Farzane , Seuberlich Torsten , Karabulut Burak , Incili Canan Akdeniz , Kara Emel , Eroksuz Hatice
Published: June 2024

Background

This study presents the case of non‐purulent encephalomyelitis associated with astrovirus infection in a sheep from Eastern Anatolia, Türkiye.

Methods

A necropsy was performed on a sheep showing nervous signs. Afterwards, brain tissue samples were taken and examined with histopathological, immunohistochemical and molecular techniques.

Results

Neuropathologic changes included neuronal degeneration, diffuse gliosis, multifocal perivascular cuffing, neuronophagy and neuronal necrosis in the cerebrum, the cerebellum and the cervical spinal cord. Aerobic and anaerobic bacterial culture, selective culture for Listeria monocytogenes, and PCR analysis for rabies virus, tick‐borne encephalitis virus, Türkiye encephalitis virus, small ruminant lentiviruses and border disease virus were negative. However, the presence of astrovirus RNA in cerebral, cerebellar and spinal cord samples was demonstrated by a pan‐astrovirus RT‐PCR. Immunohistochemical examinations revealed astrovirus antigens within the neuronal cytoplasm. High‐throughput sequencing techniques identified the causative agent as a member of the genotype species Mamastrovirus 13 but representing a distinct genetic lineage with similarity to ovine astrovirus 1 in the open‐reading frames (ORF)1ab region and muskox astrovirus in the ORF2 region.

Conclusion

This report provides evidence that astroviruses are potentially encephalitis‐causing pathogens in ovine populations in Türkiye, featuring an astrovirus strain distinct from those previously identified in sheep.
NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype
Authors: Muela-Zarzuela Inés , Suarez-Rivero Juan Miguel , Gallardo-Orihuela Andrea , Wang Chun , Izawa Kumi , de Gregorio-Procopio Marta , Couillin Isabelle , Ryffel Bernhard , Kitaura Jiro , Sanz Alberto , von Zglinicki Thomas , Mbalaviele Gabriel , Cordero Mario D.
Published: June 2024

Background

Senescence is a cellular aging-related process triggered by different stresses and characterized by the secretion of various inflammatory factors referred to as senescence-associated secretory phenotype (SASP), some of which are produced by the NLRP3 inflammasome. Here, we present evidence that the NLRP1 inflammasome is a DNA damage sensor and a key mediator of senescence.

Methods

Senescence was induced in fibroblasts in vitro and in mice. Cellular senescence was assessed by Western blot analysis of several proteins, including p16, p21, p53, and SASP factors, released in the culture media or serum. Inflammasome components, including NLRP1, NLRP3 and GSDMD were knocked out or silenced using siRNAs.

Results

In vitro and in vivo results suggest that the NLRP1 inflammasome promotes senescence by regulating the expression of p16, p21, p53, and SASP factors in a Gasdermin D (GSDMD)-dependent manner. Mechanistically, the NLRP1 inflammasome is activated in response to genomic damage detected by the cytosolic DNA sensor cGMP-AMP (cGAMP) synthase (cGAS).

Conclusion

Our findings show that NLRP1 is a cGAS-dependent DNA damage sensor during senescence and a mediator of SASP release through GSDMD. This study advances the knowledge on the biology of the NLRP1 inflammasome and highlights this pathway as a potential pharmcological target to modulate senescence.
Eigenvalue Estimates on Weighted Manifolds
Authors: Branding Volker , Habib Georges
Published: June 2024

We derive various eigenvalue estimates for the Hodge Laplacian acting on differential forms on weighted Riemannian manifolds. Our estimates unify and extend various results from the literature and provide a number of geometric applications. In particular, we derive an inequality which relates the eigenvalues of the Jacobi operator for f-minimal hypersurfaces and the spectrum of the Hodge Laplacian.
Effects of different LED light curing units on the degree of conversion and microhardness of different composites: FT-IR and SEM-EDX analysis
Authors: Bilge Kübra , İpek İrem
Published: June 2024

The aim of this study was to evaluate the degree of conversion (DC), Vickers microhardness (VHN), main components and surface properties of a microhybrid and two bulk-fill composite resins polymerized with second and third generation light emitting diodes (LED). Sixty cylindrical specimens of Filtek™ Bulk-Fill, everX Posterior (bulk technique) and Filtek Z250 (incremental technique) were prepared in plexiglass molds (5 mm in diameter and 4 mm in thickness) and cured with second-generation LED (Woodpecker LED.B) and third-generation LED (Valo) resulting in six groups (n = 10). DC was determined using Fourier transform infrared spectroscopy (FT-IR), and VHN with Vickers microhardness tester. The main components were identified by means of energy-dispersive X-ray spectroscopy (EDX) microanalysis; whereas filler particles and surface properties were analyzed by scanning electron microscopy (SEM). VHN and DC data were analyzed using two-way ANOVA, followed by t-test with Bonferroni correction for pairwise comparison (p < 0.05). When DC and VHN values were evaluated, after polymerization with second and third generation LED, there was a statistical difference in bulk-fill composites, while there was no statistical difference in microhybrid composite. While, the highest DC and VHN values were obtained after polymerization of Filtek Z250 with Valo, the lowest DC and VHN values were obtained with Filtek Bulk-Fill with Woodpecker LED.B. The degree of conversion and microhardness are affected by the structure of the composite resin and LEDs.
Not every knee tumour is a ganglion - retrospective analysis of benign and malign tumour entities around the knee
Authors: Behrendt Peter , Grunow T , K-H Frosch , Krause M , Fahlbusch H , Priemel M
Published: June 2024

Background

Due to a lack of routine, there is often uncertainty regarding diagnostics of tumours around the knee joint. This study aimed to provide knowledge about the frequency, distribution and diagnostic algorithm of different bone and soft tissue tumour entities of the knee at a large referral university hospital in Germany.

Methods

Retrospective, longitudinal, single-centre study that reviewed adult patients from 2010 until 2020 with a suspected tumours diagnosis around the knee at a university cancer centre. Inclusion criteria were adults with true bone or soft-tissue tumours in the knee joint and in its adjacent compartments. Suspected diagnosis, histological tumour entity, localization and its surgical treatment by biopsy, resection, osteosynthesis or tumour endoprosthesis were investigated.

Results

A total number of 310 adult patients were included with a mean age of 54.2 ± 18.8 years. In total 160 (51.6%) soft-tissue tumours (69/43.1% benign; 74/46.2% malignant; 17/10.6% intermediate), 92 (29.6%) primary bone tumours (46/50% benign; 39/42.3% malignant; 7/7.6% intermediate), 36 (11.6%) metastases and 22 (7.1%) lymphomas were detected. 171 (55.1%) tumours were classified as malignant. Suspected diagnosis was matched with histology in 74.5% (231/310) of all cases. In 6 cases a primarily suspected benign diagnosis turned out to be malignant. The majority of primary bone tumours was cartilage derived (63.1%;58/92) and located in the distal 2/3 of the femur, whereas intracapsular tumours of the knee joint were rare (13.0%). Soft-tissue tumours were located primarily in the middle third of the thigh (36.8%). The MRI was the diagnostic tool of choice in 98.1% of soft tissue tumours and 82.6% bone tumours.

Conclusion

Awareness is crucial for detecting rare and malignant tumours around the knee, with adipocytic tumours being the most common soft tissue tumour and chondrogenic tumours as the most prevalent malignant bone tumour. Accurate diagnosis of bone tumours necessitates radiographs and frequently an additional MRI scan, while soft tissue tumours require mandatory MRI scans. Incorrectly diagnosing a tumour can have severe consequences, emphasizing the need for histological confirmation in all cases. Additionally, malignant tumours within joint capsules in adults are infrequent.
An MRI evaluation of white matter involvement in paradigmatic forms of spastic ataxia: results from the multi-center PROSPAX study
Authors: Scaravilli Alessandra , Gabusi Ilaria , Mari Gaia , Battocchio Matteo , Bosticardo Sara , Schiavi Simona , Bender Benjamin , Kessler Christoph , Brais Bernard , La Piana Roberta , van de Warrenburg Bart P. , Cosottini Mirco , Timmann Dagmar ,   PROSPAX Consortium, Daducci Alessandro , Schüle Rebecca , Synofzik Matthis , Santorelli Filippo Maria , Cocozza Sirio
Published: June 2024

Background

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia Type 7 (SPG7) are paradigmatic spastic ataxias (SPAX) with suggested white matter (WM) involvement. Aim of this work was to thoroughly disentangle the degree of WM involvement in these conditions, evaluating both macrostructure and microstructure via the analysis of diffusion MRI (dMRI) data.

Material and methods

In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA). Differences in terms of WM volume or global microstructural WM metrics were probed, as well as the possible occurrence of a spatially defined microstructural WM involvement via voxel-wise analyses, and its correlation with patients’ clinical status.

Results

Data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years), 37 SPG7 (M/F = 24/13; 55.7 ± 10.7 years), and 29 HC (M/F = 13/16; 42.1 ± 17.2 years) were analyzed. While in SPG7, only a mild mean microstructural damage was found compared to HC, ARSACS patients present a severe WM involvement, with a reduced global volume (p < 0.001), an alteration of all microstructural metrics (all with p < 0.001), without a spatially defined pattern of damage but with a prominent involvement of commissural fibers. Finally, in ARSACS, a correlation between microstructural damage and SARA scores was found (p = 0.004).

Conclusion

In ARSACS, but not SPG7 patients, we observed a complex and multi-faced involvement of brain WM, with a clinically meaningful widespread loss of axonal and dendritic integrity, secondary demyelination and, overall, a reduction in cellularity and volume.
Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis
Authors: Shenoy U. Sangeetha , Basavarajappa Dhanraj Salur , Kabekkodu Shama Prasada , Radhakrishnan Raghu
Published: June 2024

Homeodomain transcription factor A9 (HOXA9) is a member of the HOX cluster family of transcription factors that are crucially involved in embryo implantation, morphogenesis, body axis development, and endothelial cell differentiation. Despite numerous reports on its aberrant expression in a few malignancies, the molecular and functional complexity of HOXA9 across cancers remains obscure. We aimed to analyze the dynamic role of HOXA9 across cancers by identifying, analyzing, and understanding its multiple modes of regulation and functional implications and identifying possible therapeutic avenues. We conducted a comprehensive analysis to determine the role of HOXA9 across cancers. This approach involved the integration of large-scale datasets from public repositories such as the Genomic Data Commons, specifically the Cancer Genome Atlas (GDC-TCGA), across 33 different cancer types. The multiple modes of HOXA9 regulation by genetic and epigenetic factors were determined using online tools, which comprised experimentally validated observations. Furthermore, downstream pathways were identified by predicting the targets of HOXA9 and by performing functional enrichment analysis. We also assessed the clinical significance of HOXA9 in terms of prognosis and stage stratification. This study evaluated the correlation between HOXA9 and tumor-infiltrating molecules and discussed its association with therapeutically approved antineoplastic drugs. HOXA9 was significantly upregulated in 9 tumors and downregulated in 2 cancers. The deregulation of HOXA9 is primarily attributed to epigenetic factors, including promoter DNA methylation and noncoding RNAs (ncRNAs). The HOXA9 transcription factor interacts with PBX/MEIS cofactors and regulates multiple genes involved in cancer-associated EMT, autophagy, the cell cycle, metabolic pathways, Wnt signaling, TGF-β signaling, the AMPK pathway, PI3K/AKT signaling, and NF-κB signaling, thereby establishing control over downstream mechanisms. Differential expression in various clinical stages across cancers was shown to have prognostic significance and to be correlated with tumor-infiltrating immune molecules. The assessment of the correlation of HOXA9 expression with approved antineoplastic drugs revealed that targeting HOXA9 could be the most reliable strategy for preventing cancer progression. HOXA9 is upregulated in the majority of malignancies and drives cancer progression by regulating multiple signaling mechanisms. Hence, HOXA9 could be a reliable diagnostic indicator and a potential therapeutic candidate for solid cancer types.
Distance-dependent mating but considerable pollen immigration in an isolated Quercus rubra planting in Germany
Authors: Dominguez-Flores Tania , Budde Katharina B. , Carlson John E. , Gailing Oliver
Published: June 2024

Gene flow affects the genetic diversity and structure of tree species and can be influenced by stress related to changing climatic conditions. The study of tree species planted in locations outside their natural range, such as arboreta or botanical gardens, allows us to analyse the effect of severe fragmentation on patterns and distances of gene flow. Paternity analysis based on microsatellite marker genotyping was used to analyse how fragmentation affects gene flow among individuals of Quercus rubra L. distributed in a small isolated group of trees (15 trees) planted in the arboretum on the North Campus of the University of Göttingen. For paternity analysis, 365 seedlings from four seed parents were selected and genotyped using 16 microsatellites. The analysis revealed the majority of pollen (84.89%) originated from trees within the site and identified three large full-sib families consisting of 145, 63 and 51 full-sibs. The average pollen dispersal distance for the four seed parents ranged from 17.3 to 103.6 meters. We observed substantial genetic differentiation among effective pollen clouds of the four seed parents (G’’ST = 0.407) as a result of cross pollination between neighboring trees. No self-fertilization was observed. Gene dispersal via pollen followed the expected distance-dependent pattern, and we observed a significant influx of external pollen (15.11%, ranging from 8.64 to 26.26% for individual seed parents) from a diverse set of donors (30). Long-distance pollen dispersal could explain the presence of significant genetic variation even in isolated natural Q. rubra populations.
Simulation of coronary fractional flow reserve and whole-cycle flow based on optical coherence tomography in individual patients with coronary artery disease
Authors: Olsen Niels Thue , Sheng Kaining
Published: June 2024

Computer simulations of coronary fractional flow reserve (FFR) based on coronary imaging have emerged as an attractive alternative to invasive measurements. However, most methods are proprietary and employ non-physiological assumptions. Our aims were to develop and validate a physiologically realistic open-source simulation model for coronary flow, and to use this model to predict FFR based on intracoronary optical coherence tomography (OCT) data in individual patients. We included patients undergoing elective coronary angiography with angiographic borderline coronary stenosis. Invasive measurements of coronary hyperemic pressure and absolute flow and OCT imaging were performed. A computer model of coronary flow incorporating pulsatile flow and the effect of left ventricular contraction was developed and calibrated, and patient-specific flow simulation was performed. Forty-eight coronary arteries from 41 patients were included in the analysis. Average FFR was 0.79 ± 0.14, and 50% had FFR ≤ 0.80. Correlation between simulated and measured FFR was high (r = 0.83, p < 0.001). Average difference between simulated FFR and observed FFR in individual patients was − 0.009 ± 0.076. Overall diagnostic accuracy for simulated FFR ≤ 0.80 in predicting observed FFR ≤ 0.80 was 0.88 (0.75–0.95) with sensitivity 0.79 (0.58–0.93) and specificity 0.96 (0.79–1.00). The positive predictive value was 0.95 (0.75–1.00) and the negative predictive value was 0.82 (0.63–0.94). In conclusion, realistic simulations of whole-cycle coronary flow can be produced based on intracoronary OCT data with a new, computationally simple simulation model. Simulated FFR had moderate numerical agreement with observed FFR and a good diagnostic accuracy for predicting hemodynamic significance of coronary stenoses.