bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing presentations and outcomes of children with cancer: a study between a lower-middle-income country and a high-income country
Authors: Farrag Ahmed , Ghazaly Mohamed Hamdy , Mohammed Khaled , Volland Ruth , Hero Barbara , Berthold Frank
Published: September 2023

Background

Substantial progress has been achieved in managing childhood cancers in many high-income countries (HICs). In contrast, survival rates in lower-middle-income countries (LMICs) are less favorable. Here, we aimed to compare outcomes and associated factors between two large institutions; Egypt (LMIC) and Germany (HIC).

Methods

A retrospective review was conducted on newly diagnosed children with cancer between 2006 and 2010 in the departments of pediatric oncology at the South Egypt Cancer Institute (SECI) (n = 502) and the University Hospital of Cologne-Uniklinik Köln (UKK) (n = 238). Characteristics including age, sex, diagnosis, travel time from home to the cancer center, the time interval from initial symptoms to the start of treatment, treatment-related complications, compliance, and outcome were analyzed. A Cox proportional hazards regression model was applied to investigate the influence of risk factors.

Results

The most common diagnoses in SECI were leukemia (48.8%), lymphomas (24.1%), brain tumors (1%), and other solid tumors (24.7%), compared to 22.3%, 19.3%, 28.6%, and 26.5% in UKK, respectively.

Patients from SECI were younger (5.2 vs. 9.0 years, P < 0.001), needed longer travel time to reach the treatment center (1.44 ± 0.07 vs. 0.53 ± 0.03 h, P < 0.001), received therapy earlier (7.53 ± 0.59 vs. 12.09 ± 1.01 days, P = 0.034), showed less compliance (85.1% vs. 97.1%, P < 0.001), and relapsed earlier (7 vs. 12 months, P = 0.008). Deaths in SECI were more frequent (47.4% vs. 18.1%) and caused mainly by infection (60% in SECI, 7% in UKK), while in UKK, they were primarily disease-related (79% in UKK, 27.7% in SECI). Differences in overall and event-free survival were observed for leukemias but not for non-Hodgkin lymphoma.

Conclusions

Outcome differences were associated with different causes of death and other less prominent factors.
Potential of patellar height measurement methods in predicting recurrent patellar dislocation incidence: a case-control study
Authors: Yamashita Satoshi , Ishizuka Shinya , Sakai Tadahiro , Oba Hiroki , Sakaguchi Takefumi , Mizuno Takafumi , Kawashima Itaru , Tsukahara Takashi , Takahashi Shigeo , Kurokouchi Kazutoshi , Imagama Shiro
Published: September 2023

Background

Recurrent patellar dislocation (RPD) is a multifactorial disease that affects young and active people. Patellar height measurements are used clinically to screen and diagnose knee conditions. However, there are no known studies that have assessed and compared the performance of patellar height indices for predicting the incidence of RPD, which could be used to recommend surgical treatment after primary patellar dislocation. This case-control study aimed to determine if the patellar height index could be used to predict the incidence of RPD, and to identify the optimal method in terms of its diagnostic ability for RPD.

Method

Altogether, 133 patients (52 patients with RPD [Group R] and 81 sex- and age-matched controls [Group C]) were enrolled in this study. The Insall-Salvati (IS), Blackburne-Peel (BP), Caton-Deschamps (CD), and modified IS (mIS) methods were used to measure the patellar height index. The intra-observer and inter-observer reliabilities of these four methods were determined using intraclass correlation coefficients. A receiver operating characteristic curve analysis was performed to evaluate the predictive ability of each index and identify the cut-off values that indicated significantly increased risk of RPD.

Results

Patient demographics were similar between the two groups. The inter-observer and intra-observer reliabilities were good for all four methods. In patients with RPD, the mean index values for the four methods were significantly higher than those in the matched controls. The area under the curve (AUC) values for IS, BP, CD, and mIS were 0.91 (standard error [SE], 0.03; 95% confidence interval [CI], 0.84–0.96), 0.72 (SE, 0.05; 95% CI, 0.63–0.81), 0.86 (SE, 0.03; 95% CI, 0.79–0.92), and 0.96 (SE, 0.01; 95% CI, 0.94–0.99), respectively.

Conclusion

Patellar height indices had high predictive performance for the incidence of RPD. The mIS method had the highest AUC.
Professional assessment compared to patients’ attitudes toward tooth replacement: a cross-sectional study
Authors: Alalawi Haidar , Alhumaily Hasan
Published: September 2023

Background

There is a difference between patient self-assessment and professional assessment of oral health needs; therefore, the aim of the study was to investigate patients’ individual needs and awareness of replacing missing teeth with prostheses and then to compare this information with professionally assessed clinical prosthetic needs in the Eastern Province of Saudi Arabia.

Methods

This was a cross-sectional study conducted in the Eastern Province of Saudi Arabia. The study subjects were recruited from Imam Abdulrahman bin Faisal University in Dammam City, Primary Health Care Centers in Alhasa City and from health education campaigns in the same area. All the patients were provided with a questionnaire related to the effect of missing teeth and replacement options, then underwent a clinical examination performed by a well-trained investigator. Statistical analyses were performed using JMP data analysis software (JMP®, Version 16. SAS Institute Inc., Cary, NC, 1989–2021.)

Results

A total of 102 participants were included. Most of the participants (94.2%) reported their need to replace missing teeth. Most of the participants stated that losing teeth (teeth) affected their ability to chew food and their appearance (82.6% and 61.6%, respectively). Dental caries was the main reason behind teeth extraction in 77.9% of the study sample. Fixed partial prosthesis was the first treatment option preferred by 33.7%, followed by implant-supported prosthesis with 25.6% to replace the missing teeth. Only 3.5% of participants preferred not to restore the missing teeth. Professional screening showed that 48.8% of the participants had one missing anterior tooth or more, which dictates the need for esthetic restoration, and 58.1% of the participants had three missing posterior teeth or more, which dictates the need for functional restoration.

Conclusions

Patient knowledge and attitudes toward replacing missing teeth in terms of their functional and esthetic needs were variable among the population in comparison to the professional assessment of patient needs. Dentists plays a major role in raising the level of awareness about missing teeth replacement. The results of this study serve as baseline data for any related future studies.
The relationship between moral distress, ethical climate, and attitudes towards care of a dying neonate among NICU nurses
Authors: Rezaei Zeinab , Nematollahi Monirsadat , Asadi Neda
Published: September 2023

Background

Nurses working in neonatal intensive care units play a crucial role in providing care to critically ill or premature neonates. However, is not without its challenges, particularly when it comes to making difficult ethical decisions about end-of-life care. In some cases, neonates do not survive despite the best efforts of medical professionals. The present study aimed to investigate the relationship between moral distress, ethical climate, and attitudes towards end-of-life care among nurses working in neonatal intensive care units.

Methods

This is a descriptive-analytical cross-sectional study (May 21, 2021).The research population included 126 nurses working in neonatal intensive care units in Kerman province (Kerman, Jiroft, Bam, and Rafsanjan). Data collection tools included four questionnaires: demographic information, the Frommelt Attitudes towards Care of the Dying (FATCOD), the Hospital Ethical Climate Survey, and the Moral Distress Scale. SPSS22 was used to analyze the data.

Results

The results revealed that the mean frequency and intensity of moral distress were 44.42 ± 17.67 and 49.45 ± 17.11, respectively. The mean ethical climate was 92.21 ± 17.52 and the FATCOD was 89.75 ± 9.08, indicating NICU nurses’ positive perceptions of ethical climate and their favorable attitudes towards EOL care, respectively. The results showed a direct and significant relationship between ethical climate and the FATCOD (P = 0.003, r = 0.26).

Discussion

We suggest policymakers and managers design strategies for better ethical climate in hospitals and reduction of moral distress among nurses.
Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis
Authors: Noori Maryam , Yazdanpanah Niloufar , Rezaei Nima
Published: September 2023

Background

In recent years, several bispecific antibodies (BsAbs) have been introduced that revolutionized the treatment approach for patients with multiple myeloma (MM). In the present study, we sought for conducting a systematic review and meta-analysis with the aim of evaluating the safety and efficacy of BsAbs in MM patients.

Methods

PubMed, Scopus, Web of Science, and Embase databases were systematically searched on June 10, 2022. Two steps of title/abstract and full-text screening were performed for selecting the relevant articles. The primary endpoint was considered to evaluate the safety of BsAbs by examining the rate of hematologic and non-hematologic adverse effects (AEs). The secondary outcome was set at the efficacy of BsAbs through pooling objective response rate (ORR), (stringent) complete response (sCR/CR), very good partial response (VGPR), and partial response (PR).

Results

Eleven publications with a total of nine evaluable BsAbs were included for qualitative and quantitative data synthesis. Hematologic AEs were more common among patients than non-hematologic events, with the most frequent events being anemia (41.4%), neutropenia (36.4%), and thrombocytopenia (26.3%). The most common non-hematological AE was infection, which occurred in 39.9% of patients, followed by dysgeusia (28.3%), fatigue (26.5%), and diarrhea (25.8%). Besides, 8.1% of patients experienced immune effector cell-associated neurotoxicity syndrome and neurotoxicity occurred in 5.1% of them. Moreover, 59.8% of patients experienced cytokine release syndrome. The pooled rate of deaths attributable to BsAbs was estimated at 0.1%. In terms of efficacy measures, the ORR was achieved in 62.6% of MM patients, and the pooled rates of sCR/CR, VGPR, and PR were 22.7%, 23.0%, and 12.1%, respectively.

Conclusions

In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients. However, there is still room for developing BsAbs with a lower rate of AEs and capable of bypassing tumor evasion mechanisms.
Effects of soft robotic exosuit on ambulation ability in stroke patients: a systematic review
Authors: Chuang Ya-Chi , Tsai Yu-Lin , Lin Tony Tung-Liang , Ou-Yang Liang-Jun , Lee Yu-Chun , Cheng Yuan-Yang , Liu Chuan-Ching , Hsu Chun-Sheng
Published: September 2023

Background

Robot-assisted gait training is incorporated into guidelines for stroke rehabilitation. It is a promising tool combined with conventional therapy for low ambulatory patients. The heavy weight and bulky appearance of a robotic exoskeleton limits its practicality. On the other hand, soft robotic exosuit (SRE) based on its light weight and inconspicuous property, is better tolerated by patients in daily life. The aim of this study is to review the efficacy of the SRE with regard to walking ability and biomechanical properties in stroke patients.

Methods

Electronic searches were carried out in PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database. Clinical trials that investigated the effectiveness of SREs on ambulation ability in patients with post-stroke hemiparesis were eligible. Qualitative data synthesis was subsequently performed.

Results

Nine studies were identified as relevant, involving a total of 83 patients. For the assessment of SRE efficacy, outcome measures were walking ability and biomechanical properties. In terms of both immediate effect and training effect, SREs improved the walking speed, walking distance, peak ankle dorsiflexion angle during swing phase, peak paretic propulsion, stride length and compensated gait in stroke patients.

Conclusions

SRE improved the ambulation ability of stroke patients in terms of walking ability and biomechanical properties. The small number of studies limits the generalizability of interpretation. More controlled studies with better quality are required to reach a more solid conclusion on this issue.
Management of complications after skin surgery relevant for melanoma in the trunk and extremities during the COVID-19 pandemic: a case series report
Authors: Huang Yinglai , Carlsson Lena , Jogeland Karin , Samuelsson Marianne , Larsson Lars , Jonsborg Catarina
Published: September 2023

Background

Patients with melanoma have been found to be at greater risk of adverse outcomes including mortality after contacting COVID-19. Management of postsurgical complications presented additional challenges by potentially increasing exposure to COVID-19 through repeated inpatient admissions to hospital during the pandemic. We report four cases for which skin flaps, lymph ligation, and split-thickness skin graft (STSG) were successfully used in the treatment of complications in the trunk and extremities after wide local excision (WLE). This study details the operative experience in management of postsurgical complications for melanoma in the trunk and extremities during a 6-month period at the height of the COVID-19 pandemic.

Case presentation

We present 4 cases detailing management of complications that occurred after wide local excisions performed for melanoma during Feb. to Oct. 2020. Case 1: A 90-year-old man who experienced wound dehiscence and necrosis on the shoulder after non-radical excision for an aggressive melanoma and underwent the side-to-side closure after ellipse formed WLE with modified tangent-to-circle method. Case 2: An 80-year-old man who had undergone excision for melanoma in his left upper arm and histopathology did not show radically. Two weeks after the excision, he underwent a WLE and direct reconstruction with double rotation skin flap. Case 3: A 55-year-old man that experienced a large wound dehiscence on his back due to WLE. He underwent an advanced double skin flap operation. Case 4: A 36-year-old woman who had a lymphorrhea and graft necrosis after WLE and STSG on the right lower leg. A combination of micro lymph ligation and re-STSG was performed. One month after the operation, all wounds had healed. There was no clinical evidence of tumor recurrence after 8 months post procedure.

Conclusions

Severe complications (e.g., large wound dehiscence, necrosis, or lymphorrhea) following wide local excision of melanoma are infrequent but must be swiftly and appropriately managed, especially during the COVID-19 pandemic to decrease the likelihood of COVID-19 infection and impaired oncology outcomes from delaying systemic cancer therapy due to the complications in primary interventions.
Genetic polymorphisms of CYP24A1 gene and cancer susceptibility: a meta-analysis including 40640 subjects
Authors: Wang Yubin , Wang Ruiwen , Yuan Shaofei , Liu Xiaotang
Published: September 2023

Background

Whether cytochrome P450 24A1 (CYP24A1) polymorphism is associated with cancer susceptibility, the individual study results are still controversial. Therefore, we performed a comprehensive study to identify the association of CYP24A1 polymorphisms (rs4809960, rs6068816, rs2296241, rs4809957, rs2762939) with cancer susceptibility.

Methods

Electronic databases including Cochrane Library, PubMed, and Embase were systematically retrieved for relevant publications. Fixed or random-effect model was selected to calculate odds ratios (ORs) with their 95% confidence intervals (95%CI).

Results

Eighteen published articles were identified. The results indicated that rs4809960 polymorphism was associated with a decreased cancer risk in Caucasian (TT vs. TC+CC: P=0.035; C vs. T: P=0.016) and Asian population (CC vs. TC+TT: OR P=0.044; TT vs. TC+CC: P=0.021; CC vs. TT: P=0.020; C vs. T: P=0.008) and breast cancer risk (TT vs. TC+CC: P = 0.007; TC vs. TT: P=0.004; C vs. T: P=0.033). A significant association was found between rs2296241 polymorphism and esophageal squamous cell carcinoma risk (AA vs. GG+AG: P = 0.023) and prostate cancer susceptibility (A vs. G: P=0.022). Furthermore, rs4809957 polymorphism was associated with prostate cancer susceptibility in Caucasian (GG vs. GA+AA: P=0.029; GA vs. GG: P=0.022) and breast cancer susceptibility (AA vs. GG+GA: P=0.012; AA vs. GG, P=0.010; A vs. G: P=0.024). Additionally, rs6068816 polymorphism significantly decreased the lung cancer (CC vs. CT+TT: P = 0.016; TT vs. CC: P = 0.044; CT vs. CC: P = 0.036; T vs. C: P = 0.016) and breast cancer risk (TT vs. CC+CT: P = 0.043; TT vs. CC: P = 0.039). No association was found for rs2762939 polymorphism with overall cancer risk. However, for rs2296241, rs4809957, and rs6068816 polymorphisms, there were no significant differences after the Bonferroni correction.

Conclusion

The meta-analysis suggested that rs4809960 was associated with cancer risk and might be a genetic marker for predicting cancer risk. More large-scale and large-sample studies are necessary to further confirm these results.
Research capacity, motivators and barriers to conducting research among healthcare providers in Tanzania’s public health system: a mixed methods study
Authors: Kengia James T. , Kalolo Albino , Barash David , Chwa Cindy , Hayirli Tuna Cem , Kapologwe Ntuli A. , Kinyaga Ally , Meara John G. , Staffa Steven J. , Zanial Noor , Alidina Shehnaz
Published: September 2023

Background

Building health research capacity in low- and middle-income countries is essential to achieving universal access to safe, high-quality healthcare. It can enable healthcare workers to conduct locally relevant research and apply findings to strengthen their health delivery systems. However, lack of funding, experience, know-how, and weak research infrastructures hinders their ability. Understanding research capacity, engagement, and contextual factors that either promote or obstruct research efforts by healthcare workers can inform national strategies aimed at building research capacity.

Methods

We used a convergent mixed-methods study design to understand research capacity and research engagement of healthcare workers in Tanzania’s public health system, including the barriers, motivators, and facilitators to conducting research. Our sample included 462 randomly selected healthcare workers from 45 facilities. We conducted surveys and interviews to capture data in five categories: (1) healthcare workers research capacity; (2) research engagement; (3) barriers, motivators, and facilitators; (4) interest in conducting research; and (5) institutional research capacity. We assessed quantitative and qualitative data using frequency and thematic analysis, respectively; we merged the data to identify recurring and unifying concepts.

Results

Respondents reported low experience and confidence in quantitative (34% and 28.7%, respectively) and qualitative research methods (34.5% and 19.6%, respectively). Less than half (44%) of healthcare workers engaged in research. Engagement in research was positively associated with: working at a District Hospital or above (p = 0.006), having a university degree or more (p = 0.007), and previous research experience (p = 0.001); it was negatively associated with female sex (p = 0.033). Barriers to conducting research included lack of research funding, time, skills, opportunities to practice, and research infrastructure. Motivators and facilitators included a desire to address health problems, professional development, and local and international collaborations. Almost all healthcare workers (92%) indicated interest in building their research capacity.

Conclusion

Individual and institutional research capacity and engagement among healthcare workers in Tanzania is low, despite high interest for capacity building. We propose a fourfold pathway for building research capacity in Tanzania through (1) high-quality research training and mentorship; (2) strengthening research infrastructure, funding, and coordination; (3) implementing policies and strategies that stimulate engagement; and (4) strengthening local and international collaborations.
Meeting the reproductive health needs of female sex workers in Côte d’Ivoire: protecting the human right to dignified health
Authors: Elmi Nika , Marquez Nuria Gallego , Rucinski Katherine , Lyons Carrie , Turpin Gnilane , Ba Ibrahima , Turpin Nguissali , Gouane Emile , Obodou Evelyne , Diouf Daouda , Baral Stefan
Published: September 2023

The sexual and reproductive health needs of female sex workers (FSW) are often understudied and underserved in the context of HIV-related research in countries across Sub-Saharan Africa and West Africa. We assessed the lived experiences of FSW across Côte d’Ivoire to characterize unmet reproductive health needs and opportunities to address them. From February-August, 2020, ENDA Santé, Côte d’Ivoire conducted 75 in-depth interviews and 15 focus group discussions with FSW and community informants in five cities in Côte d'Ivoire. Themes that emerged included the inconsistent use of contraception services, a history of unintended pregnancies, and experiences of stigma at public healthcare facilities. Opportunities to increase the impact of both SRH and HIV services included strengthening existing HIV and family planning service integration for FSW. Taken together, the results highlight the importance of addressing the unmet reproductive health needs of FSW to both optimize the HIV response and increase the delivery of human-rights affirming sexual and reproductive health services for sex workers.
Moral lessons from residents, close relatives and volunteers about the COVID-19 restrictions in Dutch and Flemish nursing homes
Authors: Landeweer Elleke , Hovenga Nina , Noten Suzie , Vinckers Floor , Witte Jasper de , Stoop Annerieke , Zuidema Sytse
Published: September 2023

Background

During the COVID-19 outbreak in 2020, national governments took restrictive measures, such as a visitors ban, prohibition of group activities and quarantine, to protect nursing home residents against infections. As ‘safety’ prevailed, residents and close relatives had no choice but to accept the restrictions. Their perspectives are relevant because the policies had a major impact on them, but they were excluded from the policy decisions. In this study we looked into the moral attitudes of residents, close relatives and volunteers regarding the restrictions in retrospect, and what moral lessons they considered important.

Methods

We conducted 30 semi-structured interviews with residents and close relatives and one focus group meeting with volunteers working in nursing homes. Data were transcribed verbatim and analyzed inductively. Subsequently, three Socratic dialogue meetings with residents, close relatives and volunteers were organized in which first analysis outcomes were discussed and dialogues were fostered into moral lessons for future pandemics. Outcomes were combined with moral theory following an empirical bioethics design.

Results

Critical perspectives regarding the COVID-19 restrictions grew in time. Various moral values were compromised and steered moral lessons for our future. The participants recognized three moral lessons as most important. First, constructing tailored (well-balanced) solutions in practice is desirable. Second, proper recognition is needed for the caring role that close relatives fulfill in practice. Third, a responsive power distribution should be in place that includes all stakeholder perspectives who are affected by the restrictions.

Discussion

Comparing the results with moral theory strengthens the plea for inclusion of all stakeholder groups in decision-making processes. To further concretize the moral lessons, tailored solutions can be realized with the use of moral case deliberations. Proper recognition includes actions addressing moral repair and including counter-stories in the debate. Responsive power distribution starts with providing clear and trustworthy information and including all perspectives.
Comparison of four synthetic CT generators for brain and prostate MR-only workflow in radiotherapy
Authors: Autret Damien , Guillerminet Camille , Roussel Alban , Cossec-Kerloc’h Erwan , Dufreneix Stéphane
Published: September 2023

Background

The interest in MR-only workflows is growing with the introduction of artificial intelligence in the synthetic CT generators converting MR images into CT images. The aim of this study was to evaluate several commercially available sCT generators for two anatomical localizations.

Methods

Four sCT generators were evaluated: one based on the bulk density method and three based on deep learning methods. The comparison was performed on large patient cohorts (brain: 42 patients and pelvis: 52 patients). It included geometric accuracy with the evaluation of Hounsfield Units (HU) mean error (ME) for several structures like the body, bones and soft tissues. Dose evaluation included metrics like the Dmean ME for bone structures (skull or femoral heads), PTV and soft tissues (brain or bladder or rectum). A 1%/1 mm gamma analysis was also performed.

Results

HU ME in the body were similar to those reported in the literature. Dmean ME were smaller than 2% for all structures. Mean gamma pass rate down to 78% were observed for the bulk density method in the brain. Performances of the bulk density generator were generally worse than the artificial intelligence generators for the brain but similar for the pelvis. None of the generators performed best in all the metrics studied.

Conclusions

All four generators can be used in clinical practice to implement a MR-only workflow but the bulk density method clearly performed worst in the brain.
Arthroscopic scapholunate ligament repair and dorsal capsulodesis with suture anchor in acute and subacute scapholunate dissociation
Authors: Lee Yu-Cheng , Shih Yin-Chuan , Lo I-Ning , Shih Jui-Tien
Published: September 2023

Purpose

The objective of this study was to investigate the potential of arthroscopic scapholunate ligament repair and dorsal capsulodesis with suture anchor as a treatment option for patients experiencing symptomatic acute and subacute (< 3 months) scapholunate instability.

Methods

From Jan. 2017 to Jan 2020, 19 wrists with acute or subacute tears of the SL ligament with symptomatic instability were treated with arthroscopic SL repair and dorsal capsulodesis with a suture anchor. The average time from injury to operation was 8.8 weeks (range, 4–11 weeks) and the regular follow-up mean duration at our clinic was 26.5 months (range, 24–32 months). The pain score according to the visual analog scale, wrist range of motion, grip strength, radiographic outcomes and functional outcomes according to the Modified Mayo Wrist Score (MMWS) were evaluated preoperatively and postoperatively during the follow-up period.

Results

All 19 patients had rupture and dissociation of the SL ligament in the radiocarpal joint. The total arc of wrist motion in the flexion–extension plane loss averaged 5.1° (P > .01).The Wilcoxon signed-rank test was used to compare the results: grip force improved significantly with 14.7% improvement of that on the normal side (P < .01); the postoperative MMWS was significantly better than the preoperative scores (P < .01). Of 19 patients of the series, 18 patients (94.7%) achieved good or excellent results according to the MMWS and 16 patients (84.2%) resumed their previous activities. Only one patient (5.3%) had residual laxity of the scapholunate ligament joint at 15 months of follow-up.

Conclusions

At a minimum of two years of follow-up, patients with acute or subacute symptomatic dissociation of scapholunate ligament instability who underwent arthroscopic scapholunate ligament repair and dorsal capsulodesis with suture anchor treatment had satisfactory results.

Level of Evidence

Level IV, case series.
Comprehensive evaluation of carbon sequestration potential of landscape tree species and its influencing factors analysis: implications for urban green space management
Authors: Jin Shanshan , Zhang Ershan , Guo Haotian , Hu Chuanwei , Zhang Yaru , Yan Dongfeng
Published: September 2023

Background

Continuous increasing carbon dioxide (CO2) has aggravated global warming and promoted urban tree planting projects for many countries. So it’s imperative to select high carbon sequestering landscape tree species while considering their aesthetic values of urban green space.

Results

32 tree species were selected as test objects which were commonly used in landscaping in Zhengzhou, a typical northern city of China. To assess the comprehensive carbon sequestration potential of landscape tree species in different plant configuration types, we simultaneously considered their daily net carbon sequestration per unit leaf area (wCO2), daily net carbon sequestration per unit land area (WCO2) and daily net carbon sequestration of the whole plant (QCO2) through cluster analysis. Besides that, we found out the key factors affecting carbon sequestration potential of landscape tree species by redundancy analysis.

Conclusion

Populus, P Stenoptera, P. acerifolia among large arbors (LA), V odoratissimum, P. Serratifolia, S. oblata among small arbors (SA), and B sinica var. Parvifolia, B. Megistophylla, L quihoui among shrubs (S) were recommended for local urban green space management. Photosynthetic rate (Pn), crown area (CA) and leaf area index (LAI) were the key factors which affected the comprehensive carbon sequestration potential both for LA, SA and S.
Neurodegeneration or dysfunction in Phelan-McDermid syndrome? A multimodal approach with CSF and computational MRI
Authors: Jesse Sarah , Müller Hans-Peter , Huppertz Hans-Jürgen , Andres Stephanie , Ludolph Albert C. , Schön Michael , Boeckers Tobias M. , Kassubek Jan
Published: September 2023

Background

Phelan-McDermid syndrome (PMS) is a rare multisystem disease with global developmental delay and autistic features. Genetically, the disease is based on a heterozygous deletion of chromosome 22q13.3 with involvement of at least part of the SHANK3 gene or heterozygous pathogenic variants in SHANK3. Pathophysiologically, this syndrome has been regarded as a synaptopathy, but current data suggest an additional concept, since axonal functions of neurons are also impaired, thus, the specific pathophysiological processes in this disease are not yet fully understood. Since symptoms of the autism spectrum, regression, and stagnation in development occur, we investigated whether neuroinflammatory and neurodegenerative processes may also play a role. To this end, we analysed biomarkers in cerebrospinal fluid (CSF) and parameters from magnetic resonance imaging with high-resolution structural T1w volumetry and diffusion tensor imaging analysis in 19 Phelan-McDermid syndrome patients.

Results

CSF showed no inflammation but abnormalities in tau protein and amyloid-ß concentrations, however, with no typical biomarker pattern as in Alzheimer’s disease. It could be demonstrated that these CSF changes were correlated with integrity losses of the fibres in the corticospinal tract as well as in the splenium and dorsal part of the cingulum. High CSF levels of tau protein were associated with loss of integrity of fibres in the corticospinal tract; lower levels of amyloid-ß were associated with decreasing integrity of fibre tracts of the splenium and posterior cingulate gyrus. Volumetric investigations showed global atrophy of the white matter, but not the grey matter, and particularly not in temporal or mesiotemporal regions, as is typical in later stages of Alzheimer’s disease.

Conclusions

In summary, alterations of neurodegenerative CSF markers in PMS individuals could be demonstrated which were correlated with structural connectivity losses of the corticospinal tract, the splenium, and the dorsal part of the cingulum, which can also be associated with typical clinical symptoms in these patients. These findings might represent a state of dysfunctional processes with ongoing degenerative and regenerative processes or a kind of accelerated aging. This study should foster further clinical diagnostics like tau- and amyloid-PET imaging as well as novel scientific approaches especially in basic research for further mechanistic proof.
The metabolomic plasma profile of patients with Duchenne muscular dystrophy: providing new evidence for its pathogenesis
Authors: Xu Huayan , Cai Xiaotang , Xu Ke , Wu Qihong , Xu Bei
Published: September 2023

Background

Duchenne muscular dystrophy (DMD) is a fatal genetic muscle-wasting disease that affects 1 in 5000 male births with no current cure. Despite great progress has been made in the research of DMD, its underlying pathological mechanism based on the metabolomics is still worthy of further study. Therefore, it is necessary to gain a deeper understanding of the mechanisms or pathogenesis underlying DMD, which may reveal potential therapeutic targets and/or biomarkers.

Results

Plasma samples from 42 patients with DMD from a natural history study and 40 age-matched healthy volunteers were subjected to a liquid chromatography-mass spectrometry-based non-targeted metabolomics approach. Acquired metabolic data were evaluated by principal component analysis, partial least squares-discriminant analysis, and metabolic pathway analysis to explore distinctive metabolic patterns in patients with DMD. Differentially expressed metabolites were identified using publicly available and integrated databases. By comparing the DMD and healthy control groups, 25 differential metabolites were detected, including amino acids, unsaturated fatty acids, carnitine, lipids, and metabolites related to the gut microbiota. Correspondingly, linoleic acid metabolism, D-glutamine and D-glutamate metabolism, glycerophospholipid metabolism, and alanine, aspartate, and glutamate metabolism were significantly altered in patients with DMD, compared with those of healthy volunteers.

Conclusions

Our study demonstrated the abnormal metabolism of amino acids, energy, and lipids in patients with DMD, consistent with pathological features, such as recurrent muscle necrosis and regeneration, interstitial fibrosis, and fat replacement. Additionally, we found that metabolites of intestinal flora were disordered in DMD patients, providing support for treatment of intestinal microbia disturbance in DMD diseases. Our study provides a new research strategy for understanding the pathogenesis of DMD.
Systematic gene therapy derived from an investigative study of AAV2/8 vector gene therapy for Fabry disease
Authors: Deng Mulan , Zhou Hongyu , He Shaomei , Qiu Haoheng , Wang Yanping , Zhao April Yuanyi , Mu Yunping , Li Fanghong , Zhao Allan Zijian
Published: September 2023

Background

Fabry disease (FD) is a progressive multisystemic disease characterized by a lysosomal enzyme deficiency. A lack of α-galactosidase A (α-Gal A) activity results in the progressive systemic accumulation of its substrates, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3), which results in renal, cardiac, and/or cerebrovascular disease and early death. Enzyme replacement therapy (ERT) is the current standard of care for FD; however, it has important limitations, including a low half-life, limited distribution, and requirement of lifelong biweekly infusions of recombinant enzymes.

Methods

Herein, we evaluated a gene therapy approach using an episomal adeno-associated viral 2/8 (AAV2/8) vector that encodes the human GLA cDNA driven by a liver-specific expression cassette in a mouse model of FD that lacks α-Gal A activity and progressively accumulates Gb3 and Lyso-Gb3 in plasma and tissues.

Results

A pharmacology and toxicology study showed that administration of AAV2/8-hGLA vectors (AAV2/8-hGLA) in FD mice without immunosuppression resulted in significantly increased plasma and tissue α-Gal A activity and substantially normalized Gb3 and Lyso-Gb3 content.

Conclusions

Moreover, the plasma enzymatic activity of α-Gal A continued to be stably expressed for up to 38 weeks and sometimes even longer, indicating that AAV2/8-hGLA is effective in treating FD mice, and that α-Gal A is continuously and highly expressed in the liver, secreted into plasma, and absorbed by various tissues. These findings provide a basis for the clinical development of AAV2/8-hGLA.
An overview of mouse models of hepatocellular carcinoma
Authors: Zheng Hua-chuan , Xue Hang , Yun Wen-Jing
Published: September 2023

Hepatocellular carcinoma (HCC) has become a severe burden on global health due to its high morbidity and mortality rates. However, effective treatments for HCC are limited. The lack of suitable preclinical models may contribute to a major failure of drug development for HCC. Here, we overview several well-established mouse models of HCC, including genetically engineered mice, chemically-induced models, implantation models, and humanized mice. Immunotherapy studies of HCC have been a hot topic. Therefore, we will introduce the application of mouse models of HCC in immunotherapy. This is followed by a discussion of some other models of HCC-related liver diseases, including non-alcoholic fatty liver disease (NAFLD), hepatitis B and C virus infection, and liver fibrosis and cirrhosis. Together these provide researchers with a current overview of the mouse models of HCC and assist in the application of appropriate models for their research.
Total network controllability analysis discovers explainable drugs for Covid-19 treatment
Authors: Wei Xinru , Pan Chunyu , Zhang Xizhe , Zhang Weixiong
Published: September 2023

Background

The active pursuit of network medicine for drug repurposing, particularly for combating Covid-19, has stimulated interest in the concept of structural controllability in cellular networks. We sought to extend this theory, focusing on the defense rather than control of the cell against viral infections. Accordingly, we extended structural controllability to total structural controllability and introduced the concept of control hubs. Perturbing any control hub may render the cell uncontrollable by exogenous stimuli like viral infections, so control hubs are ideal drug targets.

Results

We developed an efficient algorithm to identify all control hubs, applying it to a largest homogeneous network of human protein interactions, including interactions between human and SARS-CoV-2 proteins. Our method recognized 65 druggable control hubs with enriched antiviral functions. Utilizing these hubs, we categorized potential drugs into four groups: antiviral and anti-inflammatory agents, drugs acting on the central nervous system, dietary supplements, and compounds enhancing immunity. An exemplification of our approach’s effectiveness, Fostamatinib, a drug initially developed for chronic immune thrombocytopenia, is now in clinical trials for treating Covid-19. Preclinical trial data demonstrated that Fostamatinib could reduce mortality rates, ICU stay length, and disease severity in Covid-19 patients.

Conclusions

Our findings confirm the efficacy of our novel strategy that leverages control hubs as drug targets. This approach provides insights into the molecular mechanisms of potential therapeutics for Covid-19, making it a valuable tool for interpretable drug discovery. Our new approach is general and applicable to repurposing drugs for other diseases.
Characterisation and comparative genomics of three new Varanus-associated Borrelia spp. from Indonesia and Australia
Authors: Gofton Alexander William , Popa-Baez Angel , Takano Ai , Soennichsen Kari , Michie Michelle , Short Makenna , Supriyono Supriyono , Pascoe Jack , Cusbert Sue , Mulley Robert
Published: September 2023

Background

Borrelia are important disease-causing tick- and louse-borne spirochaetes than can infect a wide variety of vertebrates, including humans and reptiles. Reptile-associated (REP) Borrelia, once considered a peculiarity, are now recognised as a distinct and important evolutionary lineage, and are increasingly being discovered worldwide in association with novel hosts. Numerous novel Borrelia spp. associated with monitor lizards (Varanus spp.) have been recently identified throughout the Indo-Pacific region; however, there is a lack of genomic data on these Borrelia.

Methods

We used metagenomic techniques to sequence almost complete genomes of novel Borrelia spp. from Varanus varius and Varanus giganteus from Australia, and used long- and short-read technologies to sequence the complete genomes of two strains of a novel Borrelia sp. previously isolated from ticks infesting Varanus salvator from Indonesia. We investigated intra- and interspecies genomic diversity, including plasmid diversity and relatedness, among Varanus-associated Borrelia and other available REP Borrelia and, based on 712 whole genome orthologues, produced the most complete phylogenetic analysis, to the best of our knowledge, of REP Borrelia to date.

Results

The genomic architecture of Varanus-associated Borrelia spp. is similar to that of Borrelia spp. that cause relapsing fever (RF), and includes a highly conserved megaplasmid and numerous smaller linear and circular plasmids that lack structural consistency between species. Analysis of PF32 and PF57/62 plasmid partitioning genes indicated that REP Borrelia plasmids fall into at least six distinct plasmid families, some of which are related to previously defined Borrelia plasmid families, whereas the others appear to be unique. REP Borrelia contain immunogenic variable major proteins that are homologous to those found in Borrelia spp. that cause RF, although they are limited in copy number and variability and have low sequence identities to RF variable major proteins. Phylogenetic analyses based on single marker genes and 712 single copy orthologs also definitively demonstrated the monophyly of REP Borrelia as a unique lineage.

Conclusions

In this work we present four new genomes from three novel Borrelia, and thus double the number of REP Borrelia genomes publicly available. The genomic characterisation of these Borrelia clearly demonstrates their distinctiveness as species, and we propose the names Borrelia salvatorii, ‘Candidatus Borrelia undatumii’, and ‘Candidatus Borrelia rubricentralis’ for them.

Graphical Abstract
Integrated transcriptomic and proteomic analyses of plerocercoid and adult Spirometra mansoni reveal potential important pathways in the development of the medical tapeworm
Authors: Wang Rui Jie , Li Wen , Liu Shi Nan , Wang Si Yao , Jiang Peng , Wang Zhong Quan , Zhang Xi
Published: September 2023

Background

Spirometra mansoni can parasitize animals and humans through food and water, causing parasitic zoonosis. Knowledge of the developmental process of S. mansoni is crucial for effective treatment; thus, it is important to characterize differential and specific proteins and pathways associated with parasite development.

Methods

In this study, we performed a comparative proteomic analysis of the plerocercoid and adult stages using a tandem mass tag-based quantitative proteomic approach. Additionally, integrated transcriptomic and proteomic analyses were conducted to obtain the full protein expression profiles of different life cycle stages of the tapeworm.

Results

Approximately 1166 differentially expressed proteins (DEPs) were identified in adults versus plerocercoids, of which 641 DEPs were upregulated and 525 were downregulated. Gene Ontology (GO), Clusters of Orthologous groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that most DEPs related to genetic information processing and metabolism of energy in adults seem to be more activated. In the plerocercoid stage, compared to metabolism, genetic information processing appears more dynamic. Protein-protein interaction (PPI) revealed six key proteins (phosphomannomutase, glutathione transferase, malate dehydrogenase, cytoplasmic, 40S ribosomal protein S15, ribosomal protein L15 and 60S acidic ribosomal protein P2) that may play active roles in the growth and development of S. mansoni. Finally, the combination of transcriptomic and proteomic data suggested that three pathways (ubiquitin-mediated proteolysis, phagosome and spliceosome) and five proteins closely related to these pathways might have a significant influence in S. mansoni.

Conclusions

These findings contribute to increasing the knowledge on the protein expression profiles of S. mansoni and provide new insights into functional studies on the molecular mechanisms of the neglected medical tapeworm.

Graphical Abstract
Differential sensitivity of the 2020 revised comprehensive diagnostic criteria and the 2019 ACR/EULAR classification criteria across IgG4-related disease phenotypes: results from a Norwegian cohort
Authors: Vikse Jens , Midtvedt Øyvind , Fevang Bjørg-Tilde Svanes , Garen Torhild , Palm Øyvind , Wallenius Marianne , Bakland Gunnstein , Norheim Katrine Brække , Molberg Øyvind , Hoffmann-Vold Anna-Maria
Published: September 2023

Background

We investigated sensitivity of the 2020 Revised Comprehensive Diagnostic Criteria (RCD) and the 2019 ACR/EULAR classification criteria across the four identified IgG4-related disease (IgG4-RD) phenotypes: “Pancreato-Hepato-Biliary”, “Retroperitoneum and Aorta”, “Head and Neck-limited” and “Mikulicz’ and Systemic” in a well-characterized patient cohort.

Methods

We included adult patients diagnosed with IgG4-RD after comprehensive clinical assessment at Oslo University Hospital in Norway. We assigned patients to IgG4-RD phenotypes based on pattern of organ involvement and assessed fulfillment of RCD and 2019 ACR/EULAR classification criteria. Differences between phenotype groups were analyzed using one-way ANOVA for continuous variables, and contingency tables for categorical variables.

Results

The study cohort included 79 IgG4-RD patients assigned to the “Pancreato-Hepato-Biliary” (22.8%), Retroperitoneum and Aorta” (22.8%) “Head and Neck-limited” (29.1%), and “Mikulicz’ and Systemic” (25.3%) phenotype groups, respectively. While 7﻿2/79 (91.1%) patients in total fulfilled the RCD, proportion differed across phenotype groups and was lowest in the “Retroperitoneum and Aorta” group (﻿66.7%, p < 0.001). Among the 57 (72.2%) patients meeting the 2019 ACR/EULAR classification criteria, proportion was again lowest in the “Retroperitoneum and Aorta” group (27.8%, p < 0.001).

Conclusion

The results from this study indicate that IgG4-RD patients having the “Retroperitoneum and Aorta” phenotype less often fulfill diagnostic criteria and classification criteria than patients with other IgG4-RD phenotypes. Accordingly, this phenotype is at risk of being systematically selected against in observational studies and randomized clinical trials, with potential implications for patients, caregivers and future definitions of IgG4-RD.