bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability of serum CYFRA 21 − 1 and its susceptibility to clinical characteristics in individuals without cancer: a 4-year retrospective analysis
Authors: Minamibata Asami , Kono Yoshihito , Arimoto Taichiro , Marunaka Yoshinori , Takayama Koichi
Published: September 2023

Background

CYFRA 21 − 1 is a useful marker for diagnosing and monitoring lung cancer. However, its stability remains unclear. Moreover, while its applicability to screening is now being investigated, CYFRA 21 − 1 levels in individuals without cancer, who are targets for cancer screening, have not yet been the focus of research. Therefore, the present study investigated variability in and the factors increasing serum CYFRA 21 − 1 levels.

Methods

This retrospective study recruited 951 individuals undergoing annual medical examinations for six years. We used data obtained in the first four years. Variability in serum CYFRA 21 − 1 levels over a period of four years were investigated. CYFRA 21 − 1 was categorized as normal (≤ 3.5 ng/ml) or elevated (> 3.5 ng/ml). The rate of an elevated level in one visit and the transition from an elevated to normal level between visits were visualized. A multiple logistic regression model was used to study the relationships between the frequency of elevated CYFRA 21 − 1 levels and clinical characteristics, such as age, sex, body mass index, weight changes, and the smoking status.

Results

Approximately 5% of subjects had elevated CYFRA 21 − 1 levels once in five tests over four years, while 15% had elevated CYFRA 21 − 1 levels once or more. Among subjects with elevated CYFRA 21 − 1 levels in one blood test, between 63 and 72% had normal levels in the next test. The median CYFRA 21 − 1 level in subjects with elevations in one blood test significantly decreased in the next test at all four time points. The frequency of elevated CYFRA 21 − 1 levels was associated with an older age [odds ratio (OR) = 6.99, 95% confidence interval (CI) = 3.01–16.2], current heavy smoking (OR = 3.46, 95% CI = 1.52–7.9), and weight loss (OR = 1.86, 95% CI = 1.07–3.24).

Conclusions

Variability in and the factors increasing serum CYFRA 21 − 1 levels beyond the cut-off value need to be considered when interpretating CYFRA 21 − 1 test results. The future application of CYFRA 21 − 1 to lung cancer screening may require more than a single measurement.
Location and extent of cavernous transformation of the portal vein dictates different visceral side revascularization in Meso-Rex bypass
Authors: Tang Rui , Wu Guangdong , Yu Qiang , Tong Xuan , Meng Xiangfei , Hou Yucheng , Huang Xin , Aini Abudusalamu , Yu Lihan , Duan Weidong , Lu Qian , Yan Jun
Published: September 2023

Background

As an emerging standard of care for portal vein cavernous transformation (PVCT), Meso-Rex bypass (MRB) has been complicated and variated. The study aim was to propose a new classification of PVCT to guide MRB operations.

Methods

Demographic data, the extent of extrahepatic PVCT, surgical methods for visceral side revascularization, intraoperative blood loss, operating time, changes in visceral venous pressure before and after MRB, postoperative complications and the condition of bypass vessels after MRB were extracted retrospectively from the medical records of 19 patients.

Results

The median age of the patients (13 males and 6 females) was 32.5 years, while two patients were underage. Causes of PVCT can be summarized as follows: thrombophilia such as dysfunction of antithrombin III or proteins C; secondary to abdominal surgeries; secondary to abdominal infection or traumatic intestinal obstruction, and unknown causes. Intraoperatively, the median operation time was 9.5 h (7–13 h), and the intraoperative blood loss was 300 mL (100-1,600 mL). Ten cases used autologous blood vessels while 10 used allogeneic blood vessels. The vascular anastomosis was divided into the following types according to the site and approach: Type (T) 1-PV pedicel type, T2-confluence type, T3-major visceral vascular type; and T4-collateral visceral vascular type. Furthermore, the visceral venous pressure before and after MRB dropped significantly from 36 cmH2O (28–44) to 24.5 cmH2O (15–31) (P < 0.01). Postoperatively, one patient had delayed wound healing, two developed biochemical pancreatic fistulae, one experienced lymphatic leakage, the former caused by heat damage of the pancreatic tissues, the latter by cutting lymphatic vessels in the mesentery or removing the local lymph nodes during the process of separating the superior mesenteric vein, and one was re-operated on for an intervening intestinal fistulae. Postoperative enhanced CT scans revealed a significant improvement in abdominal varix in the patients with patent bypass, and at the 1-year postoperative follow-up, enhanced CT scans of six patients showed that the long axis of the spleen was reduced by ≥ 2 cm.

Conclusions

MRB can effectively reduce visceral venous pressure in patients with PVCT. It is feasible to determine the PVCT type according to the extent of involvement and to choose individualized visceral side revascularization performances.
A cross-sectional study from NHANES found a positive association between obesity with bone mineral density among postmenopausal women
Authors: Yuan Yu , Liao Jiaxin , Luo Zhiyuan , Li Dingshuang , Hou Lei
Published: September 2023

Purpose

Obesity has been demonstrated to improve bone mineral density (BMD), according to previous research. Nevertheless, there is a dearth of clarity regarding the optimal body mass index (BMI) and waist circumference (WC) for achieving the highest beneficial BMD in postmenopausal women. The objective of this study was to establish the correlation between obesity and BMD.

Methods

The relationship between BMI, WC, and BMD was examined by using multivariate logistic regression models, fitting smoothing curves and utilizing the latest data from the National Health and Nutrition Examination Survey (NHANES) survey conducted between 2007 and 2018. Furthermore, the analysis of saturation effects was employed to examine the association of nonlinear connections among BMI, WC, and BMD.

Results

The research examined information from a combination of 564 participants. A significant correlation between BMD and BMI as well as WC was observed in our findings. The enduring correlation between BMI and WC with BMD was demonstrated across subgroup analyses categorized by age and race, except among other Hispanic and other race. Furthermore, the smoothing curve fitting indicated that there existed not just a linear correlation among BMI, WC, and BMD, but also a saturation threshold in the association of these three factors.

Conclusions

Based on our study, we have found a strong and positive relationship between obesity and BMD. According to the results of this research, maintaining obesity at a moderate level in postmenopausal women would result in achieving an optimal equilibrium between obesity and BMD.
Application of a practice-based approach in variable selection for a prediction model development study of hospital-induced delirium
Authors: Snigurska Urszula A. , Ser Sarah E. , Solberg Laurence M. , Prosperi Mattia , Magoc Tanja , Chen Zhaoyi , Bian Jiang , Bjarnadottir Ragnhildur I. , Lucero Robert J.
Published: September 2023

Background

Prognostic models of hospital-induced delirium, that include potential predisposing and precipitating factors, may be used to identify vulnerable patients and inform the implementation of tailored preventive interventions. It is recommended that, in prediction model development studies, candidate predictors are selected on the basis of existing knowledge, including knowledge from clinical practice. The purpose of this article is to describe the process of identifying and operationalizing candidate predictors of hospital-induced delirium for application in a prediction model development study using a practice-based approach.

Methods

This study is part of a larger, retrospective cohort study that is developing prognostic models of hospital-induced delirium for medical-surgical older adult patients using structured data from administrative and electronic health records. First, we conducted a review of the literature to identify clinical concepts that had been used as candidate predictors in prognostic model development-and-validation studies of hospital-induced delirium. Then, we consulted a multidisciplinary task force of nine members who independently judged whether each clinical concept was associated with hospital-induced delirium. Finally, we mapped the clinical concepts to the administrative and electronic health records and operationalized our candidate predictors.

Results

In the review of 34 studies, we identified 504 unique clinical concepts. Two-thirds of the clinical concepts (337/504) were used as candidate predictors only once. The most common clinical concepts included age (31/34), sex (29/34), and alcohol use (22/34). 96% of the clinical concepts (484/504) were judged to be associated with the development of hospital-induced delirium by at least two members of the task force. All of the task force members agreed that 47 or 9% of the 504 clinical concepts were associated with hospital-induced delirium.

Conclusions

Heterogeneity among candidate predictors of hospital-induced delirium in the literature suggests a still evolving list of factors that contribute to the development of this complex phenomenon. We demonstrated a practice-based approach to variable selection for our model development study of hospital-induced delirium. Expert judgement of variables enabled us to categorize the variables based on the amount of agreement among the experts and plan for the development of different models, including an expert-model and data-driven model.
Fat mass: a novel digital biomarker for remote monitoring that may indicate risk for malnutrition and new complications in decompensated cirrhosis
Authors: Gananandan K. , Thomas V. , Woo W. L. , Boddu R. , Kumar R. , Raja M. , Balaji A. , Kazankov K. , Mookerjee R. P.
Published: September 2023

Background

Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care.

Methods

A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing’s bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed.

Results

73.3% (11/15) patients were male with a median age of 63 (52–68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031).

Conclusions

This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.
The perceptions and attitudes of obstetric staff and midwives towards perinatal mental health disorders screening: a qualitative exploratory study in Shenzhen, China
Authors: Xiao Xiao , Ma Haixia , Zhu Shening , Li Qiaomeng , Chen Yu
Published: September 2023

Background

The perinatal period is a crucial time for women, as they experience various biological, psychological, and social stressors. Due to the complexity of this vulnerable time, there is a high prevalence of depressive and anxiety disorders among pregnant women. In 2019, the Health Commission of Shenzhen initiated perinatal mental health screening programme in China. However, attitudes and perceptions of medical staff towards implementing mental health screening programme during pregnancy remain unclear. The aim of this study was to explore the perceptions and attitudes of obstetric staff and midwives towards screening for perinatal mental disorders in pregnant women, and identify their perceived needs and motivations for undertaking this task.

Methods

This is a qualitative exploratory study. Data were collected through in-depth, semi-structured, face-to-face interviews. The dataset was analysed using inductive content analysis. Purposive sampling method was used to recruit 13 participants at a tertiary maternal hospital in Shenzhen from September to November, 2019.

Results

A total of 13 obstetric staff was interviewed, including two obstetricians, three midwives, and eight nurses. Four themes were identified from this study: views on perinatal mental health disorders screening, competency in identifying and supporting high-risk groups, barriers to dealing with psychological problems during pregnancy, and the support needs of medical staff in undertaking the tasks of mental health disorders screening.

Conclusion

Medical staff lacked sufficient knowledge and skills in perinatal psychological health and were not well prepared for the task of screening pregnant women for mental health disorders. To address this issue, medical organisations and relevant government sectors should provide training to medical staff on perinatal mental health disorders, enhance public awareness of perinatal mental health disorders, establish a model of multidisciplinary collaboration for the screening of women’s perinatal mental disorders, and provide continuous and holistic care for pregnant women.
The impact of anti-malarial markets on artemisinin resistance: perspectives from Burkina Faso
Authors: Guissou Rosemonde M. , Amaratunga Chanaki , de Haan Freek , Tou Fatoumata , Cheah Phaik Yeong , Yerbanga R. Serge , Moors Ellen H. M. , Dhorda Mehul , Tindana Paulina , Boon Wouter P. C. , Dondorp Arjen M. , Ouédraogo Jean Bosco
Published: September 2023

Background

Widespread artemisinin resistance in Africa could be catastrophic when drawing parallels with the failure of chloroquine in the 1970s and 1980s. This article explores the role of anti-malarial market characteristics in the emergence and spread of arteminisin resistance in African countries, drawing on perspectives from Burkina Faso.

Methods

Data were collected through in-depth interviews and focus group discussions. A representative sample of national policy makers, regulators, public and private sector wholesalers, retailers, clinicians, nurses, and community members were purposively sampled. Additional information was also sought via review of policy publications and grey literature on anti-malarial policies and deployment practices in Burkina Faso.

Results

Thirty seven in-depth interviews and 6 focus group discussions were conducted. The study reveals that the current operational mode of anti-malarial drug markets in Burkina Faso promotes arteminisin resistance emergence and spread. The factors are mainly related to the artemisinin-based combination therapy (ACT) supply chain, to ACT quality, ACT prescription monitoring and to ACT access and misuse by patients.

Conclusion

Study findings highlight the urgent requirement to reform current characteristics of the anti-malarial drug market in order to delay the emergence and spread of artemisinin resistance in Burkina Faso. Four recommendations for public policy emerged during data analysis: (1) Address the suboptimal prescription of anti-malarial drugs, (2) Apply laws that prohibit the sale of anti-malarials without prescription, (3) Restrict the availability of street drugs, (4) Sensitize the population on the value of compliance regarding correct acquisition and intake of anti-malarials. Funding systems for anti-malarial drugs in terms of availability and accessibility must also be stabilized.
Feasibility and anteversion accuracy of a patient-specific instrument for femoral prosthesis implantation in total hip arthroplasty
Authors: Zheng Wei , Liu Xuefeng , Mei Runhong , Deng Gaorong , Li Zhipeng , Lin Rongji , Xiong Shui , Wu Binghua
Published: September 2023

Background

The aim of this study was to evaluate the precision and feasibility of patient-specific instruments (PSI) in total hip arthroplasty (THA) as compared to the traditional free-hand (FRH) approach.

Methods

During the period of January 1, 2021 to December 31, 2022, a randomized allocation was used for patients receiving unilateral primary THA to either the PSI or conventional operation group. The placement and size of the PSI were specifically chosen to guide femoral neck resection and prosthesis implantation. The study analyzed component positions and evaluated radiographic and clinical outcomes in 30 patients who received PSI-assisted THAs and 30 patients who received FRH THAs. This study was registered at China Clinical Trial Registry (number: ChiCTR2300072325) on June 9th, 2023.

Results

The use of PSI in THA resulted in significantly higher precision in achieving the desired component position as compared to the FRH approach. The PSI group showed significantly smaller absolute errors of femoral anteversion (p < 0.001). No significant differences were found in operation time, intra-operative blood loss, hospitalization duration, or time to walk after surgery.

Conclusion

In conclusion, the application of patient-specific instruments in THA provides a simple and reliable solution to enhance the precision of femoral prosthesis placement with high accuracy and feasibility. This study highlights the potential benefits of using the PSI in THA.
Efficacy and safety of totally laparoscopic gastrectomy with uncut Roux-en-Y for gastric cancer: a dual-center retrospective study
Authors: Chen Yizhen , Zheng Yuanyuan , Tan Song , Chen Yifan , Zheng Tao , Liu Shaolin , Mi Yulong , Lin Shentao , Yang Changshun , Jiang Jian , Li Weihua
Published: September 2023

Background

Uncut Roux-en-Y (URY) effectively alleviates the prevalent complexities connected with RY, such as Roux-en-Y stasis syndrome (RSS). Nevertheless, for gastric cancer (GC) patients, it is still controversial whether URY has an impact on long-term prognosis and whether it has fewer afferent loop recanalization. Therefore, compare whether URY and RY have differences in prognosis and long-term complications of GC patients undergoing totally laparoscopic gastrectomy (TLG).

Methods

We analyzed the data of patients who underwent TLG combined with digestive tract reconstruction from dual-center between 2016 and 2022. Only patients undergoing URY and RY were selected for analysis. Relapse-free survival (RFS) and overall survival (OS) were estimated. Bias between the groups was reduced by propensity score matching (PSM). The Cox proportional hazard regression model was used to further analyze the influence of URY on prognosis.

Results

Two hundred forty two GC patients were enrolled. The URY had significantly shorter operation time, liquid food intake time, and in-hospital stays than the RY (P < 0.001). The URY had fewer long-term and short-term postoperative complications than the RY, especially with regard to RSS, reflux esophagitis, and reflux gastritis. The 3-year and 5-year OS of the URY group and the RY group before PSM: 87.5% vs. 65.6% (P < 0.001) and 81.4% vs. 61.7% (P = 0.001). PSM and Cox multivariate analysis confirmed that compared to RY, URY can improve the short-term and long-term prognosis of GC patients.

Conclusion

TLG combined with URY for GC, especially for advanced, older, and poorly differentiated patients, may promote postoperative recovery and improve long-term prognosis.
Operative vs. conservative treatment of AC-Joint Dislocations Rockwood grade ≥ III -An economical and clinical evaluation-
Authors: Niehaus Richard , Schleicher Alisa , Ammann Elias , Kriechling Philipp , Lenz Christopher G. , Masanneck Michael , Hodel Sandro , Eid Karim
Published: September 2023

Introduction

Acromioclavicular joint dislocations (ACD) are one of the most common shoulder injuries. There is no consensus in how to treat higher graded ACD ≥ Rockwood grade III. This study compares operative versus conservative treatment regarding costs and clinical outcome parameters.

Materials and Methods

This retrospective, consecutive case-control-study includes 14 patients. Seven operatively treated patients were matched, by Rockwood grade, with seven conservatively treated patients. The cost was extracted out of the clinical- and insurance-based cost sheets and furthermore these include the loss of earnings. Clinical examination, demographic data as well as different outcome-questionnaires were recorded.

Results

There were no significant differences between operative and conservative treated patients for outcome Questionnaires. Of note, there was a significantly higher incidence of tenderness over the AC-joint (p = 0.0038) postoperatively. As expected, economical evaluation showed various findings in favor of the conservative treatment. The costs for medical services (11012.39vs.1163.81USD; p = 0.0061), days of hospitalization (3.3vs.0days; p < 0.0001); total cost for medical treatment (30262.17 vs. 7833.82 USD; p = 0.0358) were significantly higher in the operative group.

Conclusion

Even with a limited case number and a retrospective study design almost all clinical results were equal in both groups. Operative therapy of higher graded ACDs (Rockwood > III) compared to conservative is economically inefficient. Under consideration of clinical comparable results, indications for operative treatment should be set very carefully.
Association between body fat distribution and B-lymphocyte subsets in peripheral blood
Authors: Prechtl Pia , Schmitz Timo , Pochert Nicole , Traidl-Hoffmann Claudia , Linseisen Jakob , Meisinger Christa , Freuer Dennis
Published: September 2023

Background

Obesity is associated with chronic low-grade inflammation, which is underpinned by the presence of elevated levels of circulating proinflammatory cytokines in obese individuals. Due to the close relationship between adipose tissue and the immune system, it can be speculated that the accumulation of fat may influence the frequency and phenotype of lymphocyte populations. The aim of our study was to investigate whether body fat distribution is associated with B lymphocyte composition in peripheral blood. We examined the association between visceral (VAT) and total body fat (TBF) and the frequencies of B-cell subsets in 238 subjects over a period of up to one year using random intercept models. B lymphocyte subsets were determined by fluorescence-based flow cytometry.

Results

Inverse associations were found between body fat measurements and plasma blasts, memory B cells, and IgM−IgD− cells. VAT, but not TBF, was positively associated with naive CD19 cells. In our analyses, both VAT and TBF showed positive associations with IgD only B cells.

Conclusions

In conclusion, body fat accumulation seems to be associated with a lower proportion of antibody-secreting plasma blasts and memory cells and an increasing amount of partially anergic, naive CD19 cells.
Efficacy and safety of carbon ion radiotherapy for chordomas: a systematic review and meta-analysis
Authors: Dong Meng , Liu Ruifeng , Zhang Qiuning , Wang Dandan , Luo Hongtao , Wang Yuhang , Chen Junru , Ou Yuhong , Wang Xiaohu
Published: September 2023

Objective

Carbon ion radiotherapy (C-ion RT) for chordomas has been gradually performed in several research centres. This study aimed to systematically review the results of clinical reports from these institutions and to evaluate the safety and efficacy of C-ion RT.

Methods

In accordance with the PRISMA guidelines and set search strategies, we searched four databases for articles from their inception to February 11, 2023. These articles were screened, and data were extracted independently by two researchers. STATA 14.0 was used for statistical analysis of survival results.

Results

A total of 942 related articles were retrieved, 11 of which were included. Regarding lesion location, 57% (n = 552) originated in the sacral region, 41% (n = 398) in the skull base, and 2% (n = 19) in the spine (upper cervical). The local control (LC) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 96%, 93%, 83%, 76%, 71%, and 54%, respectively. The overall survival (OS) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 99%, 100%, 93%, 85%, 76%, and 69%, respectively. Acute and late toxicities were acceptable, acute toxicities were mainly grade 1 to grade 2 and late toxicities were mainly grade 1 to grade 3.

Conclusion

C-ion RT has attractive clinical application prospects and is an important local treatment strategy for chordomas. Encouraging results were observed in terms of LC and OS. Meanwhile, the acute and late toxicities were acceptable.

PROSPERO registration number: CRD42023398792.
Research trends of radiation induced temporal lobe injury in patients with nasopharyngeal carcinoma from 2000 to 2022: a bibliometric analysis
Authors: Guan Ying , Yu Bin-Bin , Liu Shuai , Luo Han-Ying , Huang Shi-Ting
Published: September 2023

Background

In patients with nasopharyngeal cancer (NPC), radiation-induced temporal lobe injury (TLI) is the most dreaded late-stage complication following radiation therapy (RT). We currently lack a definitive algorithmic administration for this entity. In the meantime, the pathogenesis of TLI and the mechanism-based interventions to prevent or treat this adverse effect remain unknown. To better answer the aforementioned questions, it is necessary to comprehend the intellectual foundations and prospective trends of this field through bibliometric analysis.

Methods

Articles were gathered from the Web of Science Core Collection (WoSCC) database between 2000 and 2022. CiteSpace was utilized to create a country/institutional co-authorship network, perform dual-map analysis, and find keywords with citation bursts. VOSviewer was used to build networks based on author co-authorship, journal citation, co-citation analysis of authors, references, and journals, and keyword co-occurrence.

Results

A total of 140 articles and reviews were included in the final analysis. The number of publications has steadily increased with some fluctuations over the years. The country and institution contributing most to this field are the China and Sun Yat-Sen University. Han Fei was the most prolific author, while Lee Awm was the most frequently cited. The analysis of co-occurrence revealed three clusters, including: “radiation-induced injury or necrosis in NPC,” “clinical studies on chemotherapy/radiotherapy complications and survival in recurrent NPC,” and “IMRT/chemotherapy outcomes and toxicities in head and neck cancer”). Most recent keyword bursts were “volume,” “temporal lobe injury,” “toxicities,” “model,” “survival,” “intensity modulated radiotherapy,” “induced brain injury,” “head and neck cancer,” and “temporal lobe.”

Conclusion

This study provides some insights of the major areas of interest in the field of radiation-induced TLI in patients with NPC by bibliometric analyses. This study assists scholars in locating collaborators and significant literature in this field, provides guidance for publishing journals, and identifies research hotspots. This analysis acknowledges significant contributions to the discipline and encourages the scientific community to conduct additional research.
Limited intercarpal fusion versus proximal row carpectomy in the treatment of SLAC or SNAC wrist, results after 3.5 years
Authors: Gvozdenovic Robert , Schioedt Martina Agerskov , Solgaard Lars , Vadstrup Lars Soelberg , Soee Niels Henrik
Published: September 2023

The present study compares the postoperative clinical, radiological, and patient-reported functional results between the surgical procedures Proximal Row Carpectomy and Limited Carpal Fusion, in the treatment of SLAC and SNAC conditions of the wrist. 15 Proximal Row Carpectomy patients and 45 Limited Carpal Fusion patients were included in the study. Postoperative outcomes were assessed and compared for pain at load, range of motion, grip strength, Quick-DASH, and satisfaction. A radiological assessment was performed at the follow-up. The Proximal Row Carpectomy patients had a mean age of 60 years (range 31–77) and a mean follow-up of 42 months. The Limited Carpal Fusion patients had a mean age of 58 years (range 35–76) and a mean follow-up of 41 months. The patients treated with Limited Carpal Fusion performed significantly better regarding pain, radial-ulnar motion, and the Quick-DASH (p = 0.002, p = 0.003, and p = 0.002), respectively. The grip strength difference between the treatment groups was stratified for gender and was found significantly better for men in the LCF-treated patients, but not different for women (p = 0.03, p = 0.26), respectively. Differences in flexion–extension between the groups were insignificant (p = 0.525). A higher conversion rate to total wrist fusion was observed in the patients treated with the Proximal Row Carpectomy. All the Proximal Row Carpectomy patients had osteoarthritis at follow-up, whereas it was seen in 19% of the Limited Carpal Fusion patients. The patient-reported satisfaction was substantially better for the Limited Carpal Fusion patients. In conclusion, among patients treated for SNAC and SLAC wrist conditions, besides the findings of flexion–extension, and grip strength which were found without difference for women the findings are in favour of Limited Carpal Fusion compared to Proximal Row Carpectomy. Further, preferably prospective studies are needed to confirm or reject our findings.

Level of evidence: Retrospective, comparative cohort study, level III.
Effects of textured insoles and elastic braces on dynamic stability in patients with functional ankle instability
Authors: Tang Yunqi , Li Xinyue , Li Yi , Liang Peiyao , Guo Xinyu , Zhang Cui , Kong Pui Wah
Published: September 2023

Background

Functional ankle instability (FAI) is a common condition that affects individuals who have experienced previous ankle sprains. Textured insoles and elastic ankle braces have been previously used as interventions to improve stability in FAI patients. However, the optimal combination of these interventions has not been fully explored. The objective of this study was to investigate the effects of different types of textured insoles and elastic ankle braces on the dynamic stability of individuals diagnosed with FAI.

Methods

The study involved 18 FAI patients who performed single‐leg landing tasks with and without wearing an eight‐band elastic ankle brace while wearing textured insoles with protrusion heights of 0 mm, 1 mm, and 2 mm. The dynamic posture stability index (DPSI) and its components in the anterior‐posterior (APSI), mediolateral (MLSI) and vertical (VSI) directions were calculated from the ground reaction force collected from the Kistler force plate during the first three seconds of the landing tasks.

Results

A significant interaction was found between textured insole type and ankle brace for DPSI (P = 0.026), APSI (P = 0.001), and VSI (P = 0.021). However, no significant interaction was observed for MLSI (P = 0.555). With elastic ankle braces, textured insoles with 1‐mm protrusions significantly enhanced anterior‐posterior, mediolateral, vertical, and overall stability compared to textured insoles with no and 2 mm protrusions (P < 0.05). Without elastic ankle braces, textured insoles with 1‐mm protrusions significantly improved the anterior‐posterior (P = 0.012) and overall stability (P = 0.014) of FAI patients compared to smooth insoles.

Conclusions

The combination of textured insoles with 1‐mm protrusion heights and an elastic ankle brace could enhance the dynamic stability of individuals with FAI, potentially mitigating the risk of ankle sprains.
Preliminary insights into RNA in CSF of pediatric SMA patients after 6 months of nusinersen
Authors: Garofalo M. , Bonanno S. , Marcuzzo S. , Pandini C. , Scarian E. , Dragoni F. , Di Gerlando R. , Bordoni M. , Parravicini S. , Gellera C. , Masson R. , Dosi C. , Zanin R. , Pansarasa O. , Cereda C. , Berardinelli A. , Gagliardi S.
Published: September 2023

Background

Spinal muscular atrophy (SMA) is a rare autosomal-recessive neurodegenerative disorder caused by mutations in survival motor neuron 1 (SMN1) gene, and consequent loss of function of SMN protein, which results in progressive loss of lower motor neurons, and muscular wasting. Antisense oligonucleotide (ASO) nusinersen (Spinraza®) modulates the pre–mRNA splicing of the SMN2 gene, allowing rebalance of biologically active SMN. It is administered intrathecally via lumbar puncture after removing an equal amount of cerebrospinal fluid (CSF). Its effect was proven beneficial and approved since 2017 for SMA treatment. Given the direct effect of nusinersen on RNA metabolism, the aim of this project was to evaluate cell-free RNA (cfRNA) in CSF of SMA patients under ASOs treatment for biomarker discovery.

Methods

By RNA-sequencing approach, RNA obtained from CSF of pediatric SMA type 2 and 3 patients was processed after 6 months of nusinersen treatment, at fifth intrathecal injection (T6), and compared to baseline (T0).

Results

We observed the deregulation of cfRNAs in patients at T6 and we were able to classify these RNAs into disease specific, treatment specific and treatment dependent. Moreover, we subdivided patients into “homogeneous” and “heterogeneous” according to their gene expression pattern. The “heterogeneous” group showed peculiar activation of genes coding for ribosomal components, meaning that in these patients a different molecular effect of nusinersen is observable, even if this specific molecular response was not referable to a clinical pattern.

Conclusions

This study provides preliminary insights into modulation of gene expression dependent on nusinersen treatment and lays the foundation for biomarkers discovery.
Molecular detection of pathogens from ticks collected from dogs and cats at veterinary clinics in Finland
Authors: Zakham Fathiah , Korhonen Essi M. , Puonti Petteri T. , Castrén Robert S. , Uusitalo Ruut , Smura Teemu , Kant Ravi , Vapalahti Olli , Sironen Tarja , Kinnunen Paula M.
Published: September 2023

Background

Ticks carry microbes, some of which are pathogenic for humans and animals. To assess this One Health challenge, 342 ticks were collected from pet dogs and cats at 10 veterinary clinics in Finland as part of the European project “Protect Our Future Too”.

Methods

The tick species were identified, and ticks were screened with quantitative PCR (qPCR) for tick-borne pathogens, including Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Ehrlichia canis, Anaplasma spp., Candidatus Neoehrlichia mikurensis, tick-borne encephalitis virus (TBEV), and Babesia spp. For comparison, a subset of tick DNA (20 qPCR-positive samples) was analysed with 16S next-generation sequencing (NGS).

Results

Most ticks were Ixodes ricinus (289, 84.5%), followed by Ixodes persulcatus (51, 14.9%). One hybrid tick (I. ricinus/I. persulcatus, 0.3%) and one Rhipicephalus sanguineus tick (0.3%) were identified. We found one or more of the analysed pathogens in 17% (59/342) of the ticks. The most prevalent pathogen was B. burgdorferi s.l. (36, 10.5%), followed by Anaplasma phagocytophilum (12, 3.5%), B. miyamotoi (5, 1.5%), Babesia venatorum (4, 1.2%), and TBEV (1, 0.3%). Candidatus Neoehrlichia mikurensis DNA was amplified from three (0.9%) ticks. Ehrlichia canis was not detected. In the 16S NGS, six samples produced enough reads for the analysis. In these six samples, we confirmed all the positive qPCR findings of Borrelia spp. and Ca. N. mikurensis.

Conclusions

The high prevalence of pathogenic microorganisms in the ticks of this study emphasizes the importance of awareness of ticks and tick-borne diseases and prevention. Furthermore, the results show that veterinary surveillance can facilitate early detection of tick-borne pathogens and new tick species and draw attention to possible co-infections that should be considered both in symptomatic humans and animals after tick bites.

Graphical Abstract
Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia
Authors: Humphries Sam , Bond Danielle R. , Germon Zacary P. , Keely Simon , Enjeti Anoop K. , Dun Matthew D. , Lee Heather J.
Published: September 2023

Background

Acute myeloid leukaemia (AML) is a deadly disease characterised by the uncontrolled proliferation of immature myeloid cells within the bone marrow. Altered regulation of DNA methylation is an important epigenetic driver of AML, where the hypoxic bone marrow microenvironment can help facilitate leukaemogenesis. Thus, interactions between epigenetic regulation and hypoxia signalling will have important implications for AML development and treatment.

Main body

This review summarises the importance of DNA methylation and the hypoxic bone marrow microenvironment in the development, progression, and treatment of AML. Here, we focus on the role hypoxia plays on signalling and the subsequent regulation of DNA methylation. Hypoxia is likely to influence DNA methylation through altered metabolic pathways, transcriptional control of epigenetic regulators, and direct effects on the enzymatic activity of epigenetic modifiers. DNA methylation may also prevent activation of hypoxia-responsive genes, demonstrating bidirectional crosstalk between epigenetic regulation and the hypoxic microenvironment. Finally, we consider the clinical implications of these interactions, suggesting that reduced cell cycling within the hypoxic bone marrow may decrease the efficacy of hypomethylating agents.

Conclusion

Hypoxia is likely to influence AML progression through complex interactions with DNA methylation, where the therapeutic efficacy of hypomethylating agents may be limited within the hypoxic bone marrow. To achieve optimal outcomes for AML patients, future studies should therefore consider co-treatments that can promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow.
The spatiotemporal heterogeneity of the biophysical microenvironment during hematopoietic stem cell development: from embryo to adult
Authors: Shi Guolin , Zhang Pan , Zhang Xi , Li Jing , Zheng Xinmin , Yan Jinxiao , Zhang Nu , Yang Hui
Published: September 2023

Hematopoietic stem cells (HSCs) with the ability to self-renew and differentiate are responsible for maintaining the supply of all types of blood cells. The complex and delicate microenvironment surrounding HSCs is called the HSC niche and can provide physical, chemical, and biological stimuli to regulate the survival, maintenance, proliferation, and differentiation of HSCs. Currently, the exploration of the biophysical regulation of HSCs remains in its infancy. There is evidence that HSCs are susceptible to biophysical stimuli, suggesting that the construction of engineered niche biophysical microenvironments is a promising way to regulate the fate of HSCs in vitro and ultimately contribute to clinical applications. In this review, we introduced the spatiotemporal heterogeneous biophysical microenvironment during HSC development, homeostasis, and malignancy. Furthermore, we illustrated how these biophysical cues contribute to HSC behaviors, as well as the possible mechanotransduction mechanisms from the extracellular microenvironment into cells. Comprehending the important functions of these biophysical regulatory factors will provide novel approaches to resolve clinical problems.
Loss of Dip2b leads to abnormal neural differentiation from mESCs
Authors: Yao Mingze , Pan Yuanqing , Ren Tinglin , Yang Caiting , Lei Yu , Xing Xiaoyu , Zhang Lei , Cui Xiaogang , Zheng Yaowu , Xing Li , Wu Changxin
Published: September 2023

Background

Disco-interacting protein 2 homolog B is a member of the Dip2 family encoded by the Dip2b gene. Dip2b is widely expressed in neuro-related tissues and is essential in axonal outgrowth during embryogenesis.

Methods

Dip2b knockout mouse embryonic stem cell line was established by CRISPR/Cas9 gene-editing technology. The commercial kits were utilized to detect cell cycle and growth rate. Flow cytometry, qRT-PCR, immunofluorescence, and RNA-seq were employed for phenotype and molecular mechanism assessment.

Results

Our results suggested that Dip2b is dispensable for the pluripotency maintenance of mESCs. Dip2b knockout could not alter the cell cycle and proliferation of mECSs, or the ability to differentiate into three germ layers in vitro. Furthermore, genes associated with axon guidance, channel activity, and synaptic membrane were significantly downregulated during neural differentiation upon Dip2b knockout.

Conclusions

Our results suggest that Dip2b plays an important role in neural differentiation, which will provide a valuable model for studying the exact mechanisms of Dip2b during neural differentiation.
Sox11 is enriched in myogenic progenitors but dispensable for development and regeneration of the skeletal muscle
Authors: Oprescu Stephanie N. , Baumann Nick , Chen Xiyue , Sun Qiang , Zhao Yu , Yue Feng , Wang Huating , Kuang Shihuan
Published: September 2023

Transcription factors (TFs) play key roles in regulating differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associating domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER- or Rosa26CreER- driven (MuSC-specific or global) deletion of Sox11 in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remains to be elucidated.
Optimization and characterization of antileukemic l-asparaginase produced by Fusarium solani endophyte
Authors: Osama Sarah , El-Sherei Moshera M. , Al-Mahdy Dalia A. , Bishr Mokhtar , Salama Osama , Raafat Marwa M.
Published: September 2023

l-asparaginase is an antileukemic enzyme that hydrolyzes l-asparagine into l-aspartic acid and ammonia, causing cell starvation and apoptosis in susceptible leukemic cell populations. Currently, l-asparaginase obtained from bacterial sources is constrained by several issues, including lesser productivity, stability, selectivity, and higher toxicity. The goal of this study is to provide fungal l-asparaginase with in-vitro effectiveness towards different human carcinomas. l-asparaginase from endophytic Fusarium solani (Gene Bank accession number MW209717) isolated from the roots of the medicinal plant Hedera helix L. was characterized and optimized experimentally for maximum l-asparaginase production in addition to evaluating its subsequent cytotoxicity towards acute monocytic leukemia and human skin fibroblast cell lines. The enzyme production was maximized using potato dextrose media (15.44 IU/ml/hr) at the 5th and 6th days of fermentation with incubation temperature 30 °C, 3% asparagine, 150–180 rpm agitation rate and a 250 ml flask. Enzyme characterization studies revealed that the enzyme maintained its thermal stability with temperatures up to 60 °C. However, its optimal activity was achieved at 35 °C. On measuring the enzymatic activity at various temperatures and different pH, maximum enzyme activity was recorded at 40 °C and pH 8 using 0.1 M asparagine concentration. Results also revealed promising cytotoxic activity against acute monocytic leukemia with IC50 = 3.66 µg/ml and low cytotoxicity against tested normal human skin fibroblast cell line which suggested that it might have selective toxicity, and consequently it could be used as a less toxic alternative to the current formulations.
A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1G93A model of ALS
Authors: Gerovska Daniela , Noer Julie B. , Qin Yating , Ain Quratul , Januzi Donjetë , Schwab Matthias , Witte Otto W. , Araúzo-Bravo Marcos J. , Kretz Alexandra
Published: September 2023

Background

Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function.

Methods

We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases.

Results

We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway.

Conclusions

We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention.

Graphical Abstract