bluuebunny/crossref_metadata_2025 huggingface dataset:
Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study
Authors: Zhang Yasi , Zhu Yanan , Ye Meijie , Mao Yong , Zhan Yiqiang
Published: August 2023

Objectives

To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population.

Methods

We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression.

Results

A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, p = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, p = 0.69), which does not provide evidence of the presence of horizontal pleiotropy.

Conclusions

Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.
Putting the auto in ethnography: The embodied process of reflexivity on positionality
Authors: Morrow Felicity , Kettle Martin
Published: August 2023

This article describes an unexpected methodological shift made in response to the COVID-19 pandemic during doctoral research, and exemplifies reflexivity in action whilst negotiating my complex positionality as both a researcher and a social worker. The first UK national lockdown was announced after I had conducted 3 months of ethnographic data collection in a local authority adult social work team, thus halting my research. As society shut down, face-to-face research was paused overnight, however, the local authority continued to provide essential services and support. Forging a path forward, I successfully gained a job practising as a social worker within the team and completed a supplementary ethics application to include auto-ethnographic data which would complement the existing ethnography. Although practicing reflexivity and analysing positionality are established and encouraged parts of ethnographic research, how a researcher actively conducts them varies and usually remains unseen. Methodologies are often presented in a sanitised and polished manner, depriving the reader of the messy yet informative reality of research. This article draws upon fieldnotes to practically illustrate and bring this reflexivity on positionality to the fore. As I move from participant-observer to complete-participant, the findings zoom in on my experience of navigating positionality, revealing a micro picture of the details and subtleties of this process. This unexpected research journey enhanced my level of intimacy with the phenomenon, the research site, and the participants. Overall, this example of enacting reflexivity helps to bridge the gap between how positionality is theorised and how it actively practiced. Finally, this article is a call for more open, deeper, and continual reflexivity on our positionality as researchers.
Design and implementation of the wheel-clamping stay cable inspection robot
Authors: Wang Yongming , Li Xiang , Yang Mingxing , Yin Feng
Published: August 2023

A new wheel-clamping type inspection robot for bridge stay cables was designed. Its clamping mechanism adopts a four-auxiliary-two-drive wheel clamping scheme, and the driving unit utilizes a single motor with double output shaft. A simple automatic control system of the robot was designed based on Arduino. Then, the diameter range of the stay cable that the robot can hold was calculated. The mechanical model of the robot under clamping condition was established. The curves for the minimum thrust Fe and driving force F required by the robot under different stay cable diameters Φ and inclined angles γ were obtained through Matlab data processing. Based on Adams dynamic simulation, the appropriate shape and material of the wheel, the optimal position of the centroid distribution and how to improve the wind resistance of the wheel were determined. Finally, a prototype robot was developed and a climbing experiment was carried out. The results show that the inspection robot is easy to clamp, simple to operate and control, and the detection speed is 0–5 m/min. The robot can grab stay cables with diameters ranging from 70 to 245 mm and can be used for stay cables with angles ranging from 0° to 90°.
A novel pre-bending tool for elastic stable intramedullary nailing: An efficient and accurate study
Authors: Shu Wen , Yu LongJun , Slongo Theddy , Rai Saroj , Zhong Haobo , Tang Xin
Published: August 2023

Purpose:

The elastic stable intramedullary nail has been recognized as an accepted technique for treating pediatric long bone fractures. The principle of the technique is “3-point support and fixation,” and it should be followed to achieve the optimum outcome without implant failure and complications. However, tools have yet to be reported for pre-bending of the elastic stable intramedullary nail. This study aims to present a novel tool for pre-bending the elastic stable intramedullary nails and the results of using this tool by surgeons.

Methods:

A designed case of femoral shaft fracture was provided to the participants. All participants were divided into three groups according to their experience with the elastic stable intramedullary nail technique: resident, fellow, and attending groups. The time of completing the pre-bending and coronal plane deviation of the nails after pre-bending was recorded. Statistical analysis compared the data in a conventional way and with the new tools in each group.

Results:

A total of 30 physicians were recruited in this study. The pre-bending duration with the new tool was significantly shorter than that of the conventional method for all physicians ( p < 0.001). The coronal plane deviation of nails after pre-bending by the new tool was significantly smaller than that of the conventional method for all physicians ( p < 0.001).

Conclusion:

This novel tool for elastic stable intramedullary nail pre-bending was convenient and easy to use in achieving the principal role of the elastic stable intramedullary nail technique. Physicians could reduce the coronal plane deviation when pre-bending elastic stable intramedullary nails, especially for physicians with less experience with the elastic stable intramedullary nail technique.

Level of evidence:

IV.
Exploring Loneliness in Emerging Adulthood: A Qualitative Study
Authors: Kirwan Emma M. , O’Súilleabháin Páraic S. , Burns Annette , Ogoro Mamobo , Allen Eoghan , Creaven Ann-Marie
Published: August 2023

Loneliness, the distressing feeling that accompanies the perception of a person’s social relationships as inadequate, is common in emerging adulthood. This qualitative study explored the experiences and views of loneliness, and the causes of loneliness from the perspective of emerging adults. A youth Research Advisory Group was consulted during the design of the study. Semi-structured interviews were conducted with 27 emerging adults (18–25 years old, M = 20.81, SD = 1.78). Using framework analysis, two key themes were identified; loneliness and development “ a part of growing up”, and expectations about a typical emerging adult’s life “ that’s how my life should be”. Results suggested that social transitions and expectations for an emerging adults’ life contributed to feelings of loneliness. Our findings suggest that future efforts to understand and prevent loneliness in emerging adulthood should consider that loneliness may be transient in nature and a more complex experience during this life-stage.
The 5-Factor Modified Frailty Index is Associated With Increased Risk of Reoperations and Adjacent Level Disease Following Single-Level Transforaminal Lumbar Interbody Fusion
Authors: Patel Neil , Coban Daniel , Changoor Stuart , Sinha Kumar , Hwang Ki Soo , Emami Arash
Published: August 2023

Study Design

Retrospective Cohort Study.

Objectives

To determine the predictive capability between the 5-factor modified frailty index (mFI-5) scores and adverse clinical and radiographic outcomes following single-level transforaminal lumbar interbody fusion (TLIF).

Methods

All patients over the age of 50 undergoing single-level open or minimally invasive TLIF from 2012 to 2021 with a minimum follow-up of 1 year were identified. Deformity, trauma, emergency, and tumor cases were excluded as were patients undergoing revision surgeries. An mFI-5 score was computed for each patient using a set of five factors which included hypertension requiring medication, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, and partially or fully dependent functional status. Univariate and multivariate logistic regression analysis were performed to evaluate the impact of mFI-5 scores on readmissions, reoperations, and postoperative complications.

Results

156 patients were included and grouped according to their level of frailty: no-frailty (mFI = 0, n = 67), mild frailty (mFI = 1, n = 59), and severe frailty (mFI = 2+, n = 30). Multivariate analysis found high levels of frailty (mFI = 2+) to be independent predictors of reoperation (OR: 16.9, CI: 2.7 - 106.9, P = .003) and related readmissions (OR = 16.5, CI: 2.6 - 102.7, P = .003) as compared to the no-frailty group. An mFI-5 score of 2+ was also predictive of any complication (OR = 4.5, CI: 1.4 - 14.3, P = .01) and adjacent segment disease (ASD) (OR = 12.5, CI: 1.2 - 134.0, P = .037).

Conclusion

High levels of frailty were predictive of related readmissions, reoperations, any complications, and ASD in older adult patients undergoing single-level TLIF.
Sample size requirements are not being considered in studies developing prediction models for binary outcomes: a systematic review
Authors: Dhiman Paula , Ma Jie , Qi Cathy , Bullock Garrett , Sergeant Jamie C , Riley Richard D , Collins Gary S
Published: August 2023

Background

Having an appropriate sample size is important when developing a clinical prediction model. We aimed to review how sample size is considered in studies developing a prediction model for a binary outcome.

Methods

We searched PubMed for studies published between 01/07/2020 and 30/07/2020 and reviewed the sample size calculations used to develop the prediction models. Using the available information, we calculated the minimum sample size that would be needed to estimate overall risk and minimise overfitting in each study and summarised the difference between the calculated and used sample size.

Results

A total of 119 studies were included, of which nine studies provided sample size justification (8%). The recommended minimum sample size could be calculated for 94 studies: 73% (95% CI: 63–82%) used sample sizes lower than required to estimate overall risk and minimise overfitting including 26% studies that used sample sizes lower than required to estimate overall risk only. A similar number of studies did not meet the ≥ 10EPV criteria (75%, 95% CI: 66–84%). The median deficit of the number of events used to develop a model was 75 [IQR: 234 lower to 7 higher]) which reduced to 63 if the total available data (before any data splitting) was used [IQR:225 lower to 7 higher]. Studies that met the minimum required sample size had a median c-statistic of 0.84 (IQR:0.80 to 0.9) and studies where the minimum sample size was not met had a median c-statistic of 0.83 (IQR: 0.75 to 0.9). Studies that met the ≥ 10 EPP criteria had a median c-statistic of 0.80 (IQR: 0.73 to 0.84).

Conclusions

Prediction models are often developed with no sample size calculation, as a consequence many are too small to precisely estimate the overall risk. We encourage researchers to justify, perform and report sample size calculations when developing a prediction model.
The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces
Authors: Han Jingyuan , Ma Qianli , An Yanxin , Wu Fan , Zhao Yuqing , Wu Gaoyi , Wang Jing
Published: August 2023

With the continuous innovation and breakthrough of nanomedical technology, stimuli-responsive nanotechnology has been gradually applied to the surface modification of titanium implants to achieve brilliant antibacterial activity and promoted osteogenesis. Regarding to the different physiological and pathological microenvironment around implants before and after surgery, these surface nanomodifications are designed to respond to different stimuli and environmental changes in a timely, efficient, and specific way/manner. Here, we focus on the materials related to stimuli-responsive nanotechnology on titanium implant surface modification, including metals and their compounds, polymer materials and other materials. In addition, the mechanism of different response types is introduced according to different activation stimuli, including magnetic, electrical, photic, radio frequency and ultrasonic stimuli, pH and enzymatic stimuli (the internal stimuli). Meanwhile, the associated functions, potential applications and developing prospect were discussion.
Photosensitizing deep-seated cancer cells with photoprotein-conjugated upconversion nanoparticles
Authors: Park Sung Hyun , Han Soohyun , Park Sangwoo , Kim Hyung Shik , Kim Kyung-Min , Kim Suyeon , Lee Dong Yun , Lee Joonseok , Kim Young-Pil
Published: August 2023

To resolve the problem of target specificity and light transmission to deep-seated tissues in photodynamic therapy (PDT), we report a cancer cell-targeted photosensitizer using photoprotein-conjugated upconversion nanoparticles (UCNPs) with high target specificity and efficient light transmission to deep tissues. Core-shell UCNPs with low internal energy back transfer were conjugated with recombinant proteins that consists of a photosensitizer (KillerRed; KR) and a cancer cell-targeted lead peptide (LP). Under near infrared (NIR)-irradiating condition, the UCNP-KR-LP generated superoxide anion radicals as reactive oxygen species via NIR-to-green light conversion and exhibited excellent specificity to target cancer cells through receptor-mediated cell adhesion. Consequently, this photosensitizing process facilitated rapid cell death in cancer cell lines (MCF-7, MDA-MB-231, and U-87MG) overexpressing integrin beta 1 (ITGB1) receptors but not in a cell line (SK-BR-3) with reduced ITGB1 expression and a non-invasive normal breast cell line (MCF-10A). In contrast to green light irradiation, NIR light irradiation exhibited significant PDT efficacy in cancer cells located beneath porcine skin tissues up to a depth of 10 mm, as well as in vivo tumor xenograft mouse models. This finding suggests that the designed nanocomposite is useful for sensing and targeting various deep-seated tumors.
Rivaroxaban treatment for asymptomatic venous thromboembolism: insights from the J’xactly study
Authors: Migita Shohei , Okumura Yasuo , Fukuda Ikuo , Nakamura Mashio , Yamada Norikazu , Takayama Morimasa , Maeda Hideaki , Yamashita Takeshi , Ikeda Takanori , Mo Makoto , Yamazaki Tsutomu , Hirayama Atsushi ,   on behalf of the J’xactly Investigators
Published: August 2023

Background

An established treatment strategy for asymptomatic pulmonary embolism (PE) or deep vein thrombosis (DVT) remains uncertain in Japan; therefore, in this study, we clarify the characteristics and outcomes of symptomatic compared to asymptomatic patients with PE or DVT.

Methods

This prospective, multicenter sub-analysis of the J’xactly study in Japan included 1,016 patients (mean age, 68; 41% male) with venous thromboembolism (VTE) treated with rivaroxaban.

Results

Asymptomatic PE patients (47% of PE patients) were more likely to have active cancer and asymptomatic proximal DVT at lower severity than symptomatic PE patients, despite no differences in age, sex, or the proportion receiving intensive 30 mg/day-rivaroxaban. Patients with asymptomatic DVT (34% of DVT patients) were older, had higher rates of female sex, active cancer, and distal DVT, and received shorter, less intense rivaroxaban treatment. Incidences did not differ between asymptomatic and symptomatic PE patients for recurrent symptomatic VTE (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.22–1.62; P = 0.31) or major bleeding (HR, 0.68; 95% CI, 0.20–2.33; P = 0.58), nor between asymptomatic and symptomatic DVT patients for recurrent symptomatic VTE (HR, 0.56; 95% CI, 0.23–1.40; P = 0.21) and major bleeding (HR, 1.47; 95% CI, 0.54–3.97; P = 0.45).

Conclusions

The real-world composite adverse event rate for treatment with rivaroxaban, as physician-adjusted for dose and duration, was similar for asymptomatic and symptomatic patients regardless of the presence of PE or DVT, suggesting a favorable safety profile for potential rivaroxaban treatment for asymptomatic VTE.
Uplifts and hassles are related to worsening in chronic fatigue syndrome: a prospective study
Authors: Friedberg Fred , Adamowicz Jenna L. , Bruckenthal Patricia , Milazzo Maria , Ramjan Sameera , Zhang Xiaoyue , Yang Jie
Published: August 2023

Background

Limited published data suggests that absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the relation of illness worsening to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS.

Methods

Participants were primarily in their 40s, female, white, and ill for over a decade. All participants (N = 128) met criteria for CFS. The interview-based global impression of change rating was used to classify individual outcomes as improved, unchanged, or worsened at six- month follow-up. Uplifts and hassles, both social and non-social, were assessed with the Combined Hassles and Uplifts Scale (CHUS). The CHUS was administered weekly in online diaries over six months. Linear mixed effect models were utilized to examine linear trends for hassles and uplifts.

Results

No significant differences were found between the three global outcome groups for age, sex, or illness duration; however, work status was significantly lower for the non-improved groups (p < 0.001). Non-social hassles intensity showed an increasing slope for the worsened group (p = 0.03) and a decreasing slope (p = 0.05) for the improved group. For the worsened group, a downward trend was found for frequency of non-social (p = 0.01) uplifts.

Conclusion

Individuals with worsening as compared to improving illness in CFS show significantly different six-month trajectories for weekly hassles and a deficit in uplifts. This may have clinical implications for behavioral intervention.

Trial registration ClinicalTrials.gov ID: NCT02948556.
Pancancer network analysis reveals key master regulators for cancer invasiveness
Authors: Jethalia Mahesh , Jani Siddhi P. , Ceccarelli Michele , Mall Raghvendra
Published: August 2023

Background

Tumor invasiveness reflects numerous biological changes, including tumorigenesis, progression, and metastasis. To decipher the role of transcriptional regulators (TR) involved in tumor invasiveness, we performed a systematic network-based pan-cancer assessment of master regulators of cancer invasiveness.

Materials and methods

We stratified patients in The Cancer Genome Atlas (TCGA) into invasiveness high (INV-H) and low (INV-L) groups using consensus clustering based on an established robust 24-gene signature to determine the prognostic association of invasiveness with overall survival (OS) across 32 different cancers. We devise a network-based protocol to identify TRs as master regulators (MRs) unique to INV-H and INV-L phenotypes. We validated the activity of MRs coherently associated with INV-H phenotype and worse OS across cancers in TCGA on a series of additional datasets in the Prediction of Clinical Outcomes from the Genomic Profiles (PRECOG) repository.

Results

Based on the 24-gene signature, we defined the invasiveness score for each patient sample and stratified patients into INV-H and INV-L clusters. We observed that invasiveness was associated with worse survival outcomes in almost all cancers and had a significant association with OS in ten out of 32 cancers. Our network-based framework identified common invasiveness-associated MRs specific to INV-H and INV-L groups across the ten prognostic cancers, including COL1A1, which is also part of the 24-gene signature, thus acting as a positive control. Downstream pathway analysis of MRs specific to INV-H phenotype resulted in the identification of several enriched pathways, including Epithelial into Mesenchymal Transition, TGF-β signaling pathway, regulation of Toll-like receptors, cytokines, and inflammatory response, and selective expression of chemokine receptors during T-cell polarization. Most of these pathways have connotations of inflammatory immune response and feasibility for metastasis.

Conclusion

Our pan-cancer study provides a comprehensive master regulator analysis of tumor invasiveness and can suggest more precise therapeutic strategies by targeting the identified MRs and downstream enriched pathways for patients across multiple cancers.

Graphical Abstract
The connexin hemichannel inhibitor D4 produces rapid antidepressant-like effects in mice
Authors: Li Huanhuan , Guo Anni , Salgado Magdiel , Sáez Juan C. , Lau Chunyue Geoffrey
Published: August 2023

Depression is a common mood disorder characterized by a range of clinical symptoms, including prolonged low mood and diminished interest. Although many clinical and animal studies have provided significant insights into the pathophysiology of depression, current treatment strategies are not sufficient to manage this disorder. It has been suggested that connexin (Cx)-based hemichannels are candidates for depression intervention by modifying the state of neuroinflammation. In this study, we investigated the antidepressant-like effect of a recently discovered selective Cx hemichannel inhibitor, a small organic molecule called D4. We first showed that D4 reduced hemichannel activity following systemic inflammation after LPS injections. Next, we found that D4 treatment prevented LPS-induced inflammatory response and depressive-like behaviors. These behavioral effects were accompanied by reduced astrocytic activation and hemichannel activity in depressive-like mice induced by repeated low-dose LPS challenges. D4 treatment also reverses depressive-like symptoms in mice subjected to chronic restraint stress (CRS). To test whether D4 broadly affected neural activity, we measured c-Fos expression in depression-related brain regions and found a reduction in c-Fos+ cells in different brain regions. D4 significantly normalized CRS-induced hypoactivation in several brain regions, including the hippocampus, entorhinal cortex, and lateral septum. Together, these results indicate that blocking Cx hemichannels using D4 can normalize neuronal activity and reduce depressive-like symptoms in mice by reducing neuroinflammation. Our work provides evidence of the antidepressant-like effect of D4 and supports glial Cx hemichannels as potential therapeutic targets for depression.
Contraceptive preferences and adoption following female genital fistula surgery in Uganda: a mixed-methods study
Authors: El Ayadi Alison M. , Nalubwama Hadija , Painter Caitlyn , Kakaire Othman , Miller Suellen , Barageine Justus , Byamugisha Josaphat , Obore Susan , Korn Abner , Harper Cynthia C.
Published: August 2023

Background

Female genital fistula, largely caused by prolonged obstructed labour, is treated by surgical repair. Preventing pregnancy for a minimum period post-repair is recommended to ensure adequate healing and optimize post-repair outcomes.

Methods

We examined contraceptive preferences and use among Ugandan fistula patients (n = 60) in the year following genital fistula surgery using mixed-methods. Sexual activity, contraceptive use and pregnancy status were recorded quarterly for 12 months after surgery. In-depth interviews among purposively selected participants (n = 30) explored intimate relationships, sexual experiences, reproductive intentions, and contraceptive use.

Results

Median participant age was 28 years and almost half (48%) were married or living with partners. Counselling was provided to 97% of participants on delaying sexual intercourse, but only 59% received counselling on contraception. Sexual activity was reported by 32% after 6 months and 50% after 12 months. Eighty-three percent reported not trying for pregnancy. Among sexually active participants, contraceptive use was low at baseline (36%) but increased to 73% at 12 months. Six (10%) women became pregnant including two within 3 months post-repair. Interview participants who desired children immediately were young, had fewer children, experienced stillbirth at fistula development, and felt pressure from partners. Women adopted contraception to fully recover from fistula surgery and avoid adverse outcomes. Others simply preferred to delay childbearing. Reasons cited for not adopting contraception included misconceptions related to their fertility and to contraceptive methods and insufficient or unclear healthcare provider advice on their preferred methods.

Conclusions

A high proportion of patients were not counselled by healthcare providers on contraception. Provision of comprehensive patient-centred contraceptive counselling at the time of fistula surgery and beyond is important for patients to optimize healing from fistula and minimize recurrence, as well as to meet their own reproductive preferences.
Morphology, immunohistochemistry characteristics, and clinical presentation of microcystic urothelial carcinoma: a series of 10 cases
Authors: Su Wenjing , Sui Wenwen , Cheng Xiankui , Zong Yuanyuan , Qin Yejun , Cui Fengyun
Published: August 2023

Background

Microcystic urothelial carcinoma (MUC) is a rare variant of urothelial carcinoma with histological appearances similar to begin lesions. Thus far, approximately 50 cases have been reported. Here, we investigated the clinicopathological features of MUC.

Methods

Clinical data and paraffin-embedded tissue blocks were collected. Immunohistochemical staining and polymerase chain reaction–Sanger sequencing were performed to detect the phenotype and TERT mutation status of MUC, respectively.

Results

The mean patient age was 58.8 ± 14.5 years, with a male predominance (8:2). The pathological stage was T1 in one case, T2 in three cases, T3 in four cases, and T4 in two cases. Tumor metastases or death occurred in all five patients who were followed up within 1–3 years. Histological analyses revealed microcystic, tubular, cribriform, and occasionally cord-like structures, which generally lacked interstitial reactions. The lumens were empty, contained eosinophilic secretion, or were filled with mucin. The microcysts/tubules/cribriform patterns were lined by flat, cuboid, signet ring, or columnar types of epithelia. The cuboid, signet ring, and columnar types represented “glandular metaplasia” or glandular differentiation of urothelial carcinoma. Immunohistochemistry analyses revealed distinct co-expression patterns involving the luminal markers FOXA1 and GATA3, as well as the basal markers CK5/6 and CD44. All 10 cases exhibited a luminal phenotype according to the GATA3+/CK14- criterion, whereas nine cases exhibited a luminal phenotype according to the FOXA1+/CK14- criterion. The telomerase reverse transcriptase-C228T mutation was detected in seven cases.

Conclusions

MUC is a rare variant with a deceptively benign form of urothelial carcinoma, which is generally identified as a late-stage tumor with a poor prognosis. It exhibits distinct co-expression of luminal and basal markers, along with the TERT-C228T mutation.
Fushenmu treatment ameliorates RyR2 with related metabolites in a zebrafish model of barium chloride induced arrhythmia
Authors: Zhao Yan-Ting , Liu Yan-Ru , Yan Ya-Feng , Tang Zhi-Shu , Duan Jin-Ao , Yang Hui , Song Zhong-Xing , You Xue-Lian , Wang Ming-Geng
Published: August 2023

Background

Fushenmu (Pini Radix in Poria, FSM) is a folk parasitic herb that has been mainly used for palpitation and amnesiain in traditional Chinese medicine (TCM). Recently, as an individual herb or a component of formulations, Fushenmu exhibits therapeutic potential for the treatment of cardiac arrhythmias. Yet, how specific targets or pathways of Fushenmu inhibit arrhythmia has not yet been reported.

Methods

Here, based on clinical functional genomics, metabolomics and molecular biologic technologies, a network construction strategy was adopted to identify FSM therapeutic targets and biomarkers that might explore its functions.

Results

In this study, it was found that FSM recovered arrhythmia-associated heart failure in barium chloride (BaCl2) induced arrhythmic zebrafish embryos, as was evidenced by the shortened cardiac sinus venosus—bulbus arteriosus (SV-BA) distance, smaller cardiovascular bleeding areas, and reduced cardiomyocyte apoptosis. Moreover, analysis via ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-QTOF-ESI-MS/MS) components identification and network pharmacology prediction showed that 11 main active components of FSM acted on 33 candidate therapeutic targets. Metabolomic analysis also suggested that FSM could rescue 242 abnormal metabolites from arrhythmic zebrafish embryos. Further analysis based on the combination of target prediction and metabolomic results illustrated that FSM down-regulated Ryanodine Receptor 2 (RyR2) expressions, inhibited adrenaline and 3',5'-Cyclic AMP (cAMP) levels in a dose-dependent manner, which was confirmed by metabolites quantification and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay.

Conclusion

In summary, this study revealed that FSM mitigated BaCl2 induced cardiac damage caused by arrhythmia by suppressing RyR2 expressions, decreasing adrenaline and cAMP through the adrenergic signalling pathway.
Ionic liquid-based ultrasonic-assisted extraction coupled with HPLC to analyze isoquercitrin, trifolin and afzelin in Amygdalus persica L. flowers
Authors: Zhang Wei , Yin Zhenhua , Guo Qingfeng , Chen Lin , Zhang Juanjuan
Published: August 2023

This study aimed to establish a method for the simultaneous determination of isoquercitrin, trifolin and afzelin in A. persica flowers by high performance liquid chromatography (HPLC) with ionic liquid as extractant and ultrasonic-assisted extraction. The effects of ionic liquid concentration, solid–liquid ratio, number of crushing mesh, ultrasonic time, extraction temperature, and ultrasonic power on the extraction yield of three target compounds were investigated using the extraction yield of target analytes as the index. According to the results of single factor experiment, the Box-Behnken design-response surface methodology (BBD) was used to optimize the extraction method and compared with the traditional extraction method. The results showed that, calibration curves had excellent linearity (R2 > 0.9990) within the test ranges. In combination with other validation data, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of isoquercitrin, trifolin and afzelinin A. persica flowers. And the contents of isoquercitrin, trifolin and afzelin were 64.08, 20.55 and 75.63 μg/g, respectively. The optimal process obtained by BBD was as follows: ionic liquid concentration was 1.0 mol/L, solid–liquid ratio was 1:40 g/ml, mesh sieve was 50 mesh, ultrasonic time was 40 min, extraction temperature was 50 °C, and ultrasonic power was 400 W. Under the optimal conditions, the theoretical predicted total extraction yield of the three target compounds was 159.77 μg/g, which was close to the actual extraction value (160.26 μg/g, n = 3), this result indicating that the optimal process parameters obtained by response surface methodology analysis were accurate and reliable. The method was simple, accurate and rapid for determination the contents of three active ingredients in A. persica flowers.
Evaluating the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus other treatment regimens in the chinese type 2 diabetes patients
Authors: Wei Ran , Wang Weihao , Huang Xiusheng , Qiao Jingtao , Huang Jinghe , Xing Chang , Pan Qi , Guo Lixin
Published: August 2023

Background and aims

To assess the cost-effectiveness of utilizing IDegLira in comparison to other treatment regimens ( liraglutide and degludec) in managing type 2 diabetes, taking into account the Chinese healthcare system’s perspective.

Methods

The clinical data were obtained from the randomized controlled trials (RCTs) of the DUAL I and DUAL II evidence studies that took place in China. To estimate the lifetime quality-adjusted life-years (QALYs) and direct medical costs of patients receiving different treatment strategies from a long-term perspective, the IQVIA CORE Diabetes Model version 9.0 (IQVIA, Basel, Switzerland) was utilized. The costs were evaluated from the perspective of the China National Health System. Future costs and clinical benefits were discounted annually at 5%, and sensitivity analyses were conducted.

Results

IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy (QALE) versus liraglutide and degludec. A survival benefit was observed with IDegLira over Liraglutide (0.073 years). Lifetime costs were lower by Chinese yuan (CNY) 27,945 on IDegLira than on Liraglutide therapy. A similar survival benefit was observed with IDegLira over degludec (0.068 years). Lifetime costs were lower by CNY 1196 on IDegLira than on degludec therapy. Therefore, IDegLira was found to be cost-effective versus liraglutide and degludec with incremental cost-effectiveness ratios of Dominant per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China.

Conclusion

IDegLira is a cost-effective hypoglycemic treatment option that delivers positive clinical outcomes while also reducing costs for Chinese patients living with type 2 diabetes.
Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment
Authors: Plasencia-Rodríguez Chamaida , Martínez-Feito Ana , Hernández Marta , Del Pino-Molina Lucia , Novella-Navarro Marta , Serrano Yolanda , González-Muñoz Miguel , Peiteado Diana , Bonilla Gema , Monjo Irene , Nuño Laura , Tornero Carolina , López-Granados Eduardo , Balsa Alejandro , Nozal Pilar
Published: August 2023

Background

Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients.

Material and methods

This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4–6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack.

Results

A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17–163) in patients vs 625 (405–932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%).

Conclusion

SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.
Henle fiber layer hemorrhage associated with combined central retinal vein occlusion and cilioretinal artery occlusion: a case report
Authors: Riazi-Esfahani Hamid , Ebrahimiadib Nazanin , Hamzeh Nikoo , Fadakar Kaveh , Khalili Pour Elias
Published: August 2023

Background

The purpose of this study is to describe a patient who experienced simultaneous central retinal vein and cilioretinal artery occlusions, as well as perifoveal hemorrhage in the Henle fiber.

Case presentation

A 67-year-old Iranian woman presented with a 3-day history of reduced vision in her left eye. Venous tortuosity and retinal hemorrhage were observed in the retina, together with whitened regions around the fovea, consistent with the diagnosis of central retinal vein occlusion in conjunction with cilioretinal artery occlusion. In structural and en face optical coherence tomography, star-shaped hemorrhages were observed around the fovea, which looked hyperreflective in the Henle fiber layer.

Conclusions

We present a case of central retinal vein occlusion exacerbated by cilioretinal occlusion and hemorrhage in the Henle fiber layer. The hemorrhage is most likely the result of increased intraluminal pressure in the deep capillary plexus.
Anti-pathogenicity of Acanthus ilicifolius leaf extracts against A. hydrophila infection in Labeo rohita fingerlings
Authors: Sravya M. V. N. , Simhachalam G. , Kumar N. S. Sampath , Govindarao K. , Sandeep T. Rahul , Divya D.
Published: August 2023

Antibiotic resistance has become one of the inevitable barrier in aquaculture disease management. Herbal drugs has evolved to be the novel ways of combating drug resistant pathogens. In the current investigation, leaf extracts of mangrove plant, Acanthus ilicifolius were assessed for in vitro studies, among the selected four extracts, methanol extract has expressed highest antibacterial activity against P .aeruginosa (4 ± 0.3 mm), A. hydrophila (5.9 ± 0.5 mm), S. aureus (3.5 ± 0.7 mm) and B. subtilis (2.9 ± 0.5 mm) and antioxidant activity, DPPH (81.3 ± 1.0 AAEµg/ml) and FRAP (139.1 ± 1.5 AAEµg/ml).TPC and TFC were higher in the methanolic extract and has exhibited positive correlation with both DPPH and FRAP assays. Considering the in vitro efficiency, methanol extract was purified successively by column and thin layer chromatography and characterisation by GC–MS unveiled the presence of 2-Propanethiol, Trimethylphosphine, Pentanoyl chloride, Dimethylhydroxymethylphosphine and Propanedinitrile, ethylidene. A. hydrophila infected L. rohita fingerlings has survival percentage 81% and 94% in extract treated groups over 0% in negative control and 71% in positive control.
Optimizing the extraction of essential oil from cinnamon leaf (Cinnamomum verum) for use as a potential preservative for minced beef
Authors: Yitbarek Reta Merid , Admassu Habtamu , Idris Fekiya Mohammed , Fentie Eskindir Getachew
Published: August 2023

Cinnamon leaf essential oil extraction using steam distillation method is a time-consuming and energy-intensive process. Furthermore, a lower yield and a higher rate of product degradation are this method’s main drawbacks. Thus, the goal of this research is to optimize the extraction process parameters of cinnamon leaf essential oil in response to maximizing the yield while retaining quality by using response surface methodology (RSM). The application of extracted essential oil on minced beef to assess its preservative effect was also the other objective of this research. Extraction time (120–210 min), extraction temperature (105–115 ℃), and feed mass (300–600 g) were the chosen independent variables of the optimization experiment using central composite design (CCD). Furthermore, the extracted essential oil’s antibacterial and microbiological preservative activity on minced beef was evaluated. At extraction time of 175.43 min, extraction temperature of 105 °C, and a feed mass of 600 g, the optimum predicted value of cinnamon leaf essential oil yield and cinnamaldehyde concentration (% area) was 2.9% and 34.6%, respectively. Moreover, the second-order polynomial equation fits the experimental data for 20-run experimental data. The chemical composition of cinnamon leaf essential oil extracted at optimal conditions was dominated by eugenol (60.68%) and cinnamaldehyde (33.94%). Additionally, the optimally extracted cinnamon essential oil inhibited the growth of bacteria, particularly gram-positive bacteria. After twenty-one days of storage at 4 °C, total viable count of minced beef seasoned with cinnamon essential oil at concentration of 1.2% (v/v) was lower than 106 CFU/g. To conclude, optimized cinnamon leaf essential oil extraction process provides better yield while retaining its functional properties.
Seasonal patterns in microbial carbon and iron transporter expression in the Southern Ocean
Authors: Debeljak Pavla , Bayer Barbara , Sun Ying , Herndl Gerhard J. , Obernosterer Ingrid
Published: August 2023

Background

Heterotrophic microbes in the Southern Ocean are challenged by the double constraint of low concentrations of organic carbon (C) and iron (Fe). These essential elements are tightly coupled in cellular processes; however, the prokaryotic requirements of C and Fe under varying environmental settings remain poorly studied. Here, we used a combination of metatranscriptomics and metaproteomics to identify prokaryotic membrane transporters for organic substrates and Fe in naturally iron-fertilized and high-nutrient, low-chlorophyll waters of the Southern Ocean during spring and late summer.

Results

Pronounced differences in membrane transporter profiles between seasons were observed at both sites, both at the transcript and protein level. When specific compound classes were considered, the two approaches revealed different patterns. At the transcript level, seasonal patterns were only observed for subsets of genes belonging to each transporter category. At the protein level, membrane transporters of organic compounds were relatively more abundant in spring as compared to summer, while the opposite pattern was observed for Fe transporters. These observations suggest an enhanced requirement for organic C in early spring and for Fe in late summer. Mapping transcripts and proteins to 50 metagenomic-assembled genomes revealed distinct taxon-specific seasonal differences pointing to potentially opportunistic clades, such as Pseudomonadales and Nitrincolaceae, and groups with a more restricted repertoire of expressed transporters, such as Alphaproteobacteria and Flavobacteriaceae.

Conclusion

The combined investigations of C and Fe membrane transporters suggest seasonal changes in the microbial requirements of these elements under different productivity regimes. The taxon-specific acquisition strategies of different forms of C and Fe illustrate how diverse microbes could shape transcript and protein expression profiles at the community level at different seasons. Our results on the C- and Fe-related metabolic capabilities of microbial taxa provide new insights into their potential role in the cycling of C and Fe under varying nutrient regimes in the Southern Ocean.
Real-world evidence study on tolerance and growth in infants fed an infant formula with two human milk oligosaccharides vs mixed fed and exclusively breastfed infants
Authors: Jochum Frank , Meyer-Krott Martina , Hübler Tina , Lorenz Maja , Bedikian Raffi , Zakarian Joseph , Litzka Anja , Judex Guido , Hertzberg Holger , Klee Daniela , Maurer Lothar , Schacht Martin , Al-Radhi Adnan , Maier Jan , Kröckel Alexander , Faustmann Christian , Lavalle Luca , Dahbane Samir
Published: August 2023

Introduction

Human milk oligosaccharides (HMOs) are important components of human milk having diverse functions in the development of infants. Randomized controlled trials (RCTs) have demonstrated that infant formulas with the HMOs 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) are safe, well-tolerated, and support normal growth. This study aimed to generate real-world evidence (RWE) on growth and gastrointestinal (GI) tolerance in infants consuming a formula with 1 g/L 2′FL and 0.5 g/L LNnT, including a mixed feeding group not studied before in RCTs.

Participants and methods

This 8-week open-label prospective multicenter study was conducted in Germany and Austria, and included groups of healthy, exclusively breastfed infants (BF), exclusively formula-fed infants (FF) who received the HMO-formula, and infants mixed fed with both HMO formula and human milk (MF). Co-primary outcomes were anthropometry and gastrointestinal tolerance via validated Infant Gastrointestinal Symptom Questionnaire (IGSQ). Secondary outcomes included formula satisfaction and adverse events (AEs).

Results

One-hundred six infants completed the study (46 FF, 22 MF, and 38 BF). Mean anthropometric z-scores were comparable between groups and generally within ± 0.5 of WHO medians at week 8. IGSQ composite scores demonstrated good GI tolerance in all groups with no significant group differences at week 4 or 8. IGSQ composite scores in FF improved during the course of the study and parents provided high satisfaction ratings for the HMO-formula. Four potentially product-related AEs were reported in FF (no in MF).

Conclusions

In this RWE study examining an infant formula with HMOs, growth and GI tolerance outcomes were confirming the good tolerance and safety of this early feeding option previously reported in RCTs.
Recent advances in catalytic synthesis of 2,5-furandimethanol from 5-hydroxymethylfurfural and carbohydrates
Authors: Du Ziting , Yang Delong , Cao Qingya , Dai Jinhang , Yang Ronghe , Gu Xingxing , Li Fukun
Published: August 2023

5-Hydroxymethylfurfural (HMF) is a versatile platform chemical derived from the dehydration of renewable carbohydrates (typically glucose/fructose-based monosaccharides, oligosaccharides, and polysaccharides). Some useful compounds, such as 2,5-furandimethanol (FDM), 2,5-dimethylfuran (DMF) and 2,5-dimethyltetrahydrofuran (DMTHF), have been synthesized by reduction of HMF. Among these, FDM is a promising diol and can be further converted towards fine chemicals, liquid fuels and polymer materials. In this review, some typical catalytic systems for the synthesis of FDM from both HMF and carbohydrates were summarized. The discussion focused on controlling the reaction networks for the reduction of HMF. The reaction mechanisms and the stability of the catalysts were introduced briefly. Last but not least, the prospects of effective production of FDM were discussed as well.