bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of skin and soft tissue, bone and joint infections in an Australian cohort of people who inject drugs
Authors: Morgan B. , Lancaster R. , Boyagoda B. , Ananda R. , Attwood LO , Jacka D. , Woolley I.
Published: March 2024

Introduction

There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID).

Methods

Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies.

Results

A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2–51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission.

Conclusion

Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.
Genotypic study of Chlamydia trachomatis for lymphogranuloma venereum diagnosis in rectal specimens from men who have sex with men: a cost-effectiveness analysis
Authors: Sánchez David , Ferrer Josep , Giménez Estela , Torres Ignacio , Carretero Diego , Alcaraz María Jesús , Castaño María Jesús , Navarro David , Albert Eliseo
Published: March 2024

Purpose

The significant proportion of asymptomatic patients and the scarcity of genotypic analysis of lymphogranuloma venereum (LGV), mainly among men who have sex with men (MSM), triggers a high incidence of underdiagnosed patients, highlighting the importance of determining the most appropriate strategy for LGV diagnosis, at both clinical and economical levels.

Materials and methods

We conducted L1-L3 serovar detection by molecular biology in stored Chlamydia trachomatis-positive samples from MSM patients with HIV, another STI or belonging to a Pre-exposure prophylaxis program, to make a cost effectiveness study of four diagnostic strategies with a clinical, molecular, or mixed approach.

Results

A total of 85 exudates were analyzed: 35urethral (31 symptomatic/4 positive) and 50 rectal (22 symptomatic/25 positive), 70/85 belonging to MSM with associated risk factors. The average cost per patient was €77.09 and €159.55 for clinical (Strategy I) and molecular (Strategy IV) strategies respectively. For molecular diagnosis by genotyping of all rectal exudate samples previously positive for CT (Strategy II), the cost was €123.84. For molecular diagnosis by genotyping of rectal and/or urethral exudate samples from all symptomatic patients (proctitis or urethritis) with a previous positive result for CT (Strategy III), the cost was €129.39. The effectiveness ratios were 0.80, 0.95, 0.91, and 1.00 for each strategy respectively. The smallest ICER was €311.67 for Strategy II compared to Strategy I.

Conclusions

With 30% asymptomatic patients, the most cost-effective strategy was based on genotyping all rectal exudates. With less restrictive selection criteria, thus increasing the number of patients with negative results, the most sensitive strategies tend to be the most cost-effective, but with a high incremental cost-effectiveness ratio.
Associations between anxiety, depression, and personal mastery in community-dwelling older adults: a network-based analysis
Authors: Bian Zekun , Xu Renyan , Shang Bin , Lv Fei , Sun Weiyi , Li Qian , Gong Yijing , Luo Caifeng
Published: March 2024

Background

In China, about 18.70% of the population aged 60 years and older are at risk of low personal mastery as well as anxiety and depression for a variety of reasons. The purpose of this study was to construct a symptom network model of the relationship between anxiety, depression, and personal mastery in community-dwelling older adults and to identify central and bridge symptoms in this network.

Methods

Depression, anxiety, and personal mastery were measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and Personal Mastery Scale (PMS), respectively. A total of 501 older adults in 16 communities in Changzhou and Zhenjiang, Jiangsu Province, China, were surveyed by using a combination of stratified sampling and convenience sampling methods. The R language was used to construct the network.

Results

(1) The network structure of anxiety–depression–personal mastery was stable, with “Nervousness” (node GAD1, strength = 1.38), “Sad mood” (node PHQ2, strength = 1.22), " Inability to change” (node PMS2, strength = 1.01) and “Involuntarily” (node PMS3, strength = 0.95) as the central symptoms. (2) “Irritability” (node GAD6, bridge strength = 0.743), “Sad mood” (node PHQ2, bridge strength = 0.655), and “Trouble relaxing” (node GAD4, bridge strength = 0.550) were the bridge symptoms connecting anxiety, depressive symptoms, and personal mastery. (3) In the network comparison test (NCT), residence, somatic chronic comorbidity and gender had no significant effect on network structure.

Conclusions

The construction of the anxiety–depression–personal mastery network structure opens up new possibilities for mechanisms of action and intervention formulation for psychological disorders in community-dwelling older adults. The identification of central symptoms (e.g., nervousness, sad mood, inability to change, involuntarily) and bridge symptoms (e.g., irritability, sad mood, trouble relaxing) in community-dwelling older adults with anxiety, depression, and low sense of mastery can provide a scientific basis for the development of precise interventions.
Emotional, coping factors and personality traits that influenced alcohol consumption in Romanian students during the COVID-19 pandemic. A cross-sectional study
Authors: Rada Cornelia , Faludi Cristina , Lungu Mihaela
Published: March 2024

Background

During the COVID-19 pandemic, after 3 months from the installation of the state of emergency on the territory of Romania, data were collected from 677 students and master’s students, to explore the problematic alcohol consumption (AC).

Methods

The evaluation was done with: Alcohol Use Disorders Identification Test, Depression, Anxiety and Stress Scales, Strategic Coping Approach Scale and The Freiburg Personality Inventory. The statistical methods used were linear regression with bootstrap procedure, Spearman’s rank correlation, and the Mann-Whitney U test.

Results

More than half were affected by depression or anxiety of moderate to extremely severe intensity. The prevalence of problematic alcohol consumption was low: (Hazardous and Extremely Hazardous (2.3) and Medium Risk (10.2). Early onset increases the subsequent risk of problematic AC, compared to women, men recorded a higher AC (p <.01). Anxiety, antisocial action, personality traits Aggressiveness and Somatic complaints had the effect of increasing the alcohol consumption score (p <.01). Significant but weak positive correlations between AC on one hand, and depression, anxiety, stress and antisocial action on the other hand were found (p <.01).

Conclusions

Probably the prevalence of AC was low as a result of the fact that most respondents were studying in the field of health promotion and as a result of the closure of entertainment venues. This study advocates for the education of youngsters to clearly express their opinions without violating the boundaries of others’ feelings (assertive action) and to act prudently in dangerous or uncertain situations (cautious action) since these coping mechanisms were not associated with problematic alcohol consumption. The promotion of positive, achievement-oriented, life attitudes is equally important, as these characteristics of the Life Satisfaction personality dimensions were also found as non-determinants of alcohol-induced problems. The association of problematic AC with antisocial actions as a coping mechanism and high scores on Aggressiveness calls for interventions to educate the younger generation how to acquire and adopt healthy mechanisms to control tensions without resorting to alcohol consumption, more so as the two variables reinforce each other. Drinking as a means of gaining courage must be carefully reconsidered since anxiety generally hits back, often in increased levels.
Respiratory fit test panel representing population of Malaysia
Authors: Lim Yin Cheng , Soelar Shahrul Aiman , Shakor¹ Ameerah Su’ad Abdul , Mohamad Nadia , Pahrol Muhammad Alfatih , Ismail Rohaida , Danaee Mahmoud , Shaharudin Rafiza
Published: March 2024

Background

The existing respiratory fit test panels (RFTPs) are based on Bivariate and Principal Component Analysis (PCA) which utilise American and Chinese head and facial dimensions. As RFTPs based on local facial anthropometric data for Malaysia are not available, this study was conducted with the aim to develop new RFTPs using Malaysian data.

Methodology

A cross-sectional study was conducted across Malaysia among 3,324 participants of the study of National Health and Morbidity Survey 2020 aged 18 and above. Ten head and facial dimensions were measured. Face length and face width were used to construct bivariate facial panel, whereas the scores from the first two PCA were used to develop the PCA panel.

Results

This study showed that Malaysians have the widest upper limit for facial width. It also found that three factors could be reduced from the PCA analysis. However only 2 factors were selected with PCA 1 representing head and facial size and PCA 2 representing facial shape. Our bivariate panel could accommodate 95.0% of population, while our PCA panel accommodated 95.6%.

Conclusion

This was the first study to use Malaysian head and facial anthropometry data to create bivariate and PCA panels. Respirators constructed using these panels are likely to fit ≥ 95.0% of Malaysia’s population.
The posterior tibial slope affects the measurement reliability regarding the radiographic parameter of the knee
Authors: Lee Seung-Hun , Yoo Je-Hyun , Kwak Dae-Kyung , Kim Sung-Hwan , Chae Sung-Kuk , Moon Hyun-Soo
Published: March 2024

Background

Posterior tibial slope (PTS) exhibits considerable variability among individuals and is anticipated to influence the accuracy of radiographic measurements related to the knee. Despite this potential impact, there is a lack of prior research investigating how PTS affects the accuracy of these measurements. Therefore, this study aimed to investigate the effect of PTS on the measurement reliability regarding the radiographic parameter of the knee.

Methods

The medical records of patients who took full-length anteroposterior radiographs of the lower limb between January 2020 and June 2022 were evaluated retrospectively. Radiographic parameters related to the knee joint characteristics such as osteoarthritis grade, hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle (MPTA), lateral distal femoral angle, joint-line convergence angle (JLCA), and PTS were measured. Subjects were classified into 3 groups according to PTS (group A, PTS < 4°; group B, PTS ≥ 4° and < 8°; group C, PTS ≥ 8°), and the measurement reliability for the radiographic variables was compared between groups. The intra- and inter-observer agreements were assessed using the kappa coefficients, intra-class correlation coefficients (ICC), and Bland-Altman plots.

Results

A total of 175 limbs (86 patients) were included in this study. As the intra- and inter-observer reliability for PTS ranged over 0.9, grouping was performed based on the average of the measured PTSs. The inter-observer reliability of the MPTA and JLCA decreased as the PTS increased (ICCs for MPTA in Groups A, B, and C: 0.889, 0.796, and 0.790, respectively; ICCs for JLCA in Groups A, B and C: 0.916, 0.859, and 0.843, respectively), whereas there were no remarkable differences in other variables. Similar trends were observed in the comparisons of intra-observer reliability and Bland-Altman plots also showed consistent results.

Conclusion

The larger the PTS, the lower the measurement reliability regarding the radiographic parameters of the knee that includes the joint line, such as MPTA and JLCA. Given the occasional challenge in accurately identifying the knee joint line in patients with a relatively large PTS, careful measurement of radiographic parameters is crucial and utilizing repetitive measurements for verification may contribute to minimizing measurement errors.
Free iliac crest grafting technology for the management of critical-sized tibial bone defect
Authors: Cheng Xiaoqiang , Yao Yilun , Liu Kang , Wu Lei , Yang Wengbo
Published: March 2024

Objective

To introduce the method and experience of treating critical-sized tibial bone defect by taking large iliac crest bone graft.

Methods

From January 2020 to January 2022, iliac crest bone grafting was performed in 20 patients (10 men and 10 women) with critical-sized tibial bone defect. The mean length of bone defect was 13.59 ± 3.41. Bilateral iliac crest grafts were harvested, including the inner and outer plates of the iliac crest and iliac spine. The cortical bone screw was used to integrate two iliac bone blocks into one complex. Locking plate was used to fix the graft-host complex, supplemented with reconstruction plate to increase stability when necessary. Bone healing was evaluated by cortical bone fusion on radiographs at follow-up, iliac pain was assessed by VAS score, and lower limb function was assessed by ODI score. Complications were also taken into consideration.

Results

The average follow-up time was 27.4 ± 5.6 (Range 24–33 months), the mean VAS score was 8.8 ± 1.9, the mean ODI score was 11.1 ± 1.8, and the number of cortical bone fusion in the bone graft area was 3.5 ± 0.5. Satisfactory fusion was obtained in all cases of iliac bone transplant-host site. No nonunion, shift or fracture was found in all cases. No infection and bone resorption were observed that need secondary surgery. One patient had dorsiflexion weakness of the great toe. Hypoesthesia of the dorsal foot was observed in 2 patients. Ankle stiffness and edema occurred in 3 patients. Complications were significantly improved by physical therapy and rehabilitation training.

Conclusion

For the cases of critical-sized tibial bone defect, the treatment methods are various. In this paper, we have obtained satisfactory results by using large iliac bone graft to treat bone defect. This approach can not only restore the integrity of the tibia, but also obtain good stability with internal fixation, and operation skills are more acceptable for surgeons. Therefore, it provides an alternative surgical method for clinicians.
Mind and body connection in expert meditators: a computational study based on central and peripheral nervous system
Authors: Borghesi Francesca , Cremascoli Riccardo , Chirico Alice , Bianchi Laura , Di Moia Amalia , Priano Lorenzo , Piedimonte Alessandro , Mauro Alessandro , Cipresso Pietro
Published: March 2024

A meditative ‘technique’ is conceived as a continuum of different affective states involving mind and body jointly. Meditative practices can involve cognitive effort (e.g., focused attention and open-minded techniques), as well as automatic and implicit practices (e.g., transcendental techniques). The NGALSO tantric self-healing meditation technique is a brief, comprehensive meditation technique relying on mind and body connection. In this study, we aimed to investigate the state and the trait neurophysiological correlates of NGALSO meditation practice. First, 19 EEG channels and a 3-lead ECG signal were recorded from 10 expert meditators (more than 7 years of daily meditation) and 10 healthy inexpert participants (controls) who underwent the same meditative procedure. The neuropsychological profiles of experts and controls were compared. Results showed that expert meditators had significantly higher power spectra on alpha, theta and beta, and a higher sympathetic tone with lower parasympathetic tone after meditation. Conversely, the control group had significantly less power spectra on alpha, theta and beta, and a higher parasympathetic tone with lower sympathetic tone after meditation. A machine learning approach also allowed us to classify experts vs. controls correctly by using only EEG Theta bands before or after meditation. ECG results allowed us to show a significantly higher effort by expert meditators vs. controls, thus suggesting that a higher effort is required for this meditation, in line with the principle ‘no pain, no gain’ in body and mind.
Clearing the confusion about post-accreditation monitoring, meta-evaluation and meta-accreditation
Authors: Gandomkar Roghayeh , Mirzazadeh Azim , Changiz Tahereh
Published: March 2024

We have recently published the experience of the accreditation body of undergraduate medical education in Iran on developing and validating standards based on the WFME framework (Gandomkar et al., BMC Med Educ 23:379, 2023). Agabagheri et al. extended our work and proposed a blueprint for post-accreditation monitoring based on their experience in developing an official guide in their Matters Arising (Aghabagheri et al., BMC Med Educ). The authors have used post-accreditation monitoring as a process of monitoring and controlling accreditation activities, procedures often referred to as meta-evaluation or meta-accreditation (depending on the objectives of evaluation) in the literature. On the contrary, post-accreditation monitoring alludes to the process of continuous quality improvement of educational programs after accreditation. We would like to make clarifications between post-accreditation monitoring, meta-evaluation and meta-accreditation which have been used interchangeably in their paper. Considering the emerging interests in scholarship and non-scholarship activities and reports in undergraduate medical education accreditation, this clarification provides a better understanding of the roles of these crucial concepts in the accreditation process.
Factors influencing inequality in government health expenditures within African regional economic communities
Authors: Ngepah Nicholas , Mouteyica Ariane Ephemia Ndzignat
Published: March 2024

Background

The unequal distribution of government health spending within African regional economic groupings is a significant barrier to achieving Universal Health Coverage and reaching health-related Sustainable Development targets. It also hampers the progress toward achieving the African Union’s vision of an integrated and prosperous Africa, free of its heavy disease burden. Based on panel data from 36 countries nested into eight Regional Economic Communities (RECs), this study probes the effects of countries' macro-level factors on government health expenditure disparities within eight regional economic communities from 2000 to 2019.

Method

We use the multilevel linear mixed-effect method to show whether countries' trade gains, life expectancy at birth, poverty, urbanization, information and communication technology, and population aging worsen or reduce the differences for two government health expenditure indicators.

Results

The insignificant effect of GDP per capita suggests that in most regional economic groupings, the health sector is still not considered a high-priority sector regarding overall government expenditures. Countries' poverty levels and urbanization increase the domestic general government health expenditure disparities as a percentage of general government expenditure within the regional groupings. However, trade gains and ICT diffusion reduce these disparities. Furthermore, the results reveal that external health expenditure per capita and life expectancy at birth positively impact within-regional inequalities in the domestic general government health expenditure per capita. In contrast, GDP per capita and trade gains tend to reduce them.

Conclusions

This study enriches the research on the determinants of government health expenditure inequality in Africa. Policies that can spur growth in trade and ICT access should be encouraged. Countries should also make more efforts to reduce poverty. Governments should also develop policies promoting economic growth and planned urbanization.
Anticoagulant rodenticide poisoning in farmed Patagonian mara (Dolichotis patagonum)
Authors: Chansiripornchai Piyarat , Kesdangsakonwut Sawang , Techangamsuwan Somporn
Published: March 2024

Background

Anticoagulant rodenticide (AR) poisoning was diagnosed in 3 Patagonian maras (Dolichotis patagonum) raised in the mara farm in Thailand. To date, there have been no reports of maras with diagnosed AR poisoning.

Case presentation

The first clinical sign of the sickening maras was anorexia. Fifteen from 50 maras were dead over a 3–5 day period after the clinical signs had occurred. Positive results to AR were detected in all of the maras’ liver specimens by screening test using thin layer chromatography and spectrophotometry methods. Supportive therapy was selected for the treatment of the 35 surviving maras. During the follow – up observation period of 12 months, all of the surviving maras were healthy and no reproductive loss.

Conclusions

This is the first report on suspected AR poisoning in maras in Thailand based on history taking, clinical signs, gross pathology lesions and chemical analysis. AR poisoning in the present report is possibly from contaminated animal food. Therefore, quality control of food should be fastidious when feeding maras.
Effects of hyperbaric oxygen combined cabin ventilator on critically ill patients with liberation difficulty after tracheostomy
Authors: Qi Yinliang , Xu Jixiang , Liu Hui , Zhou Xiaomei
Published: March 2024

Background

Critically ill patients undergoing liberation often encounter various physiological and clinical complexities and challenges. However, whether the combination of hyperbaric oxygen and in-cabin ventilator therapy could offer a comprehensive approach that may simultaneously address respiratory and potentially improve outcomes in this challenging patient population remain unclear.

Methods

This retrospective study involved 148 patients experiencing difficulty in liberation after tracheotomy. Inclusion criteria comprised ongoing mechanical ventilation need, lung inflammation on computed tomography (CT) scans, and Glasgow Coma Scale (GCS) scores of ≤ 9. Exclusion criteria excluded patients with active bleeding, untreated pneumothorax, cerebrospinal fluid leakage, and a heart rate below 50 beats per minute. Following exclusions, 111 cases were treated with hyperbaric oxygen combined cabin ventilator, of which 72 cases were successfully liberated (SL group) and 28 cases (NSL group) were not successfully liberated. The hyperbaric oxygen chamber group received pressurization to 0.20 MPa (2.0 ATA) for 20 min, followed by 60 min of ventilator oxygen inhalation. Successful liberation was determined by a strict process, including subjective and objective criteria, with a prolonged spontaneous breathing trial. GCS assessments were conducted to evaluate consciousness levels, with scores categorized as normal, mildly impaired, moderately impaired, or severely impaired.

Results

Patients who underwent treatment exhibited improved GCS, blood gas indicators, and cardiac function indexes. The improvement of GCS, partial pressure of oxygen (PaO2), oxygen saturation of blood (SaO2), oxygenation index (OI) in the SL group was significantly higher than that of the NSL group. However, there was no significant difference in the improvement of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and stroke volume (SV) between the SL group and the NSL group after treatment.

Conclusions

Hyperbaric oxygen combined with in-cabin ventilator therapy effectively enhances respiratory function, cardiopulmonary function, and various indicators of critically ill patients with liberation difficulty after tracheostomy.
Characterization of the proteome of stable and unstable carotid atherosclerotic plaques using data-independent acquisition mass spectrometry
Authors: Lai Zhichao , Wang Chaonan , Liu Xiaoyan , Sun Haidan , Guo Zhengguang , Shao Jiang , Li Kang , Chen Junye , Wang Jiaxian , Lei Xiangling , Shu Keqiang , Feng Yuyao , Kong Deqiang , Sun Wei , Liu Bao
Published: March 2024

Background

Currently, noninvasive imaging techniques and circulating biomarkers are still insufficient to accurately assess carotid plaque stability, and an in-depth understanding of the molecular mechanisms that contribute to plaque instability is still lacking.

Methods

We established a clinical study cohort containing 182 patients with carotid artery stenosis. After screening, 39 stable and 49 unstable plaques were included in the discovery group, and quantitative proteomics analysis based on data independent acquisition was performed for these plaque samples. Additionally, 35 plaques were included in the validation group to validate the proteomics results by immunohistochemistry analysis.

Results

A total of 397 differentially expressed proteins were identified in stable and unstable plaques. These proteins are primarily involved in ferroptosis and lipid metabolism-related functions and pathways. Plaque validation results showed that ferroptosis- and lipid metabolism-related proteins had different expression trends in stable plaques versus unstable fibrous cap regions and lipid core regions. Ferroptosis- and lipid metabolism-related mechanisms in plaque stability were discussed.

Conclusions

Our results may provide a valuable strategy for revealing the mechanisms affecting plaque stability and will facilitate the discovery of specific biomarkers to broaden the therapeutic scope.
GBA1 inactivation in oligodendrocytes affects myelination and induces neurodegenerative hallmarks and lipid dyshomeostasis in mice
Authors: Gregorio Ilaria , Russo Loris , Torretta Enrica , Barbacini Pietro , Contarini Gabriella , Pacinelli Giada , Bizzotto Dario , Moriggi Manuela , Braghetta Paola , Papaleo Francesco , Gelfi Cecilia , Moro Enrico , Cescon Matilde
Published: March 2024

Background

Mutations in the β-glucocerebrosidase (GBA1) gene do cause the lysosomal storage Gaucher disease (GD) and are among the most frequent genetic risk factors for Parkinson’s disease (PD). So far, studies on both neuronopathic GD and PD primarily focused on neuronal manifestations, besides the evaluation of microglial and astrocyte implication. White matter alterations were described in the central nervous system of paediatric type 1 GD patients and were suggested to sustain or even play a role in the PD process, although the contribution of oligodendrocytes has been so far scarcely investigated.

Methods

We exploited a system to study the induction of central myelination in vitro, consisting of Oli-neu cells treated with dibutyryl-cAMP, in order to evaluate the expression levels and function of β-glucocerebrosidase during oligodendrocyte differentiation. Conduritol-B-epoxide, a β-glucocerebrosidase irreversible inhibitor was used to dissect the impact of β-glucocerebrosidase inactivation in the process of myelination, lysosomal degradation and α-synuclein accumulation in vitro. Moreover, to study the role of β-glucocerebrosidase in the white matter in vivo, we developed a novel mouse transgenic line in which β-glucocerebrosidase function is abolished in myelinating glia, by crossing the Cnp1-cre mouse line with a line bearing loxP sequences flanking Gba1 exons 9–11, encoding for β-glucocerebrosidase catalytic domain. Immunofluorescence, western blot and lipidomic analyses were performed in brain samples from wild-type and knockout animals in order to assess the impact of genetic inactivation of β-glucocerebrosidase on myelination and on the onset of early neurodegenerative hallmarks, together with differentiation analysis in primary oligodendrocyte cultures.

Results

Here we show that β-glucocerebrosidase inactivation in oligodendrocytes induces lysosomal dysfunction and inhibits myelination in vitro. Moreover, oligodendrocyte-specific β-glucocerebrosidase loss-of-function was sufficient to induce in vivo demyelination and early neurodegenerative hallmarks, including axonal degeneration, α-synuclein accumulation and astrogliosis, together with brain lipid dyshomeostasis and functional impairment.

Conclusions

Our study sheds light on the contribution of oligodendrocytes in GBA1-related diseases and supports the need for better characterizing oligodendrocytes as actors playing a role in neurodegenerative diseases, also pointing at them as potential novel targets to set a brake to disease progression.
CT based 3D reconstruction of the forefoot’s blood supply in a white rhinoceros
Authors: Reinitz László Zoltán , Cerny Claudia , Papp Endre , Biácsi Alexandra , Fajtai Daniel , Petneházy Örs
Published: March 2024

Background

The white rhinoceros (Ceratotherium simum) is close to extinction, listed as “Near Threatened”, with a decreasing population on the Red List of Threatened Species of the International Union for Conservation of Nature. In at least 50% of the specimens in captivity, podiatric diseases, such as osteitis, osteomyelitis, chip fractures, enthesophytes, fractures and osteoarthritis were found during necropsy. These osteal deformations cause further pathogenic alterations in the soft tissues, particularly in the digital cushion. The literature provides good description of the skeleton of the rhino’s limbs, but similar for the vascular system is non-existent. In order to recognize the symptoms in an early state and for a successful surgical treatment, precise knowledge of the vascular anatomy is essential. The purpose of our study was to provide detailed anatomical description of the blood supply of the digits and that of the digital cushion.

Results

The blood supply of the distal foot, digits and digital cushions were perfectly visible on the reconstructed and coloured 3D models. The deep palmar arch provided not only the blood supply to the digits but had a palmaro-distal running branch which developed a trifurcation proximal to the proximal sesamoid bones of the third digit. Two of its branches participated in the blood supply of the digits’ proximal palmar surface, while the major branch supplied the digital cushion from proximal direction.

Conclusions

Our findings show a unique blood supply: the main vessels of the digital cushion stem both directly from the deep palmar arch and from the digits’ own arteries. The detailed description of vessels may be useful in planning surgery of the region and also in cases where the veins of the ear are not accessible.
The FBXW7-binding sites on FAM83D are potential targets for cancer therapy
Authors: Jiang Xiaoyu , Wang Yuli , Guo Lulu , Wang Yige , Miao Tianshu , Ma Lijuan , Wei Qin , Lin Xiaoyan , Mao Jian-Hua , Zhang Pengju
Published: March 2024

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.
Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities
Authors: Cha Woo-Jin , Yi Dahyun , Ahn Hyejin , Byun Min Soo , Chang Yoon Young , Choi Jung-Min , Kim Kyungtae , Choi Hyeji , Jung Gijung , Kang Koung Mi , Sohn Chul-Ho , Lee Yun-Sang , Kim Yu Kyeong , Lee Dong Young
Published: March 2024

Background

Growing evidence suggests that not only cerebrovascular disease but also Alzheimer’s disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aβ) and tau deposition, and WMHs through longitudinal approach.

Methods

Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aβ deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aβ or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aβ or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies.

Results

Baseline Aβ deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aβ or tau deposition for 2 years. We also found a significant interaction effect between baseline Aβ deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female, but not in male.

Conclusions

Our findings suggest that Aβ deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aβ increase. The results also did not support any direction of influence between tau deposition and WMHs.
Improving multi-pinhole CZT myocardial perfusion imaging specificity without changing sensibility by using adapted filter parameters
Authors: Vauchot Fabien , Dubois Julien , Bourdon Aurélie
Published: March 2024

Background

Meta-analysis show the diagnostic performance of cardiac dedicated multi-pinhole cadmium-zinc-telluride myocardial perfusion imaging (MPI) with a sensibility around 0.9 and a specificity around 0.7. The aim of the present study is to explore a simple method to generate less artefact on MPI using single photon emission computed tomography (SPECT) and to enhance specificity without changing sensibility.

Results

From October 2018 to March 2019, 200 patients who underwent SPECT with [99mTc]Tc-tetrofosmin were prospectively recruited: 100 patients with ischemia or necrosis diagnosis (first arm), and 100 patients with myocardial reversible SPECT artefact (second arm). Each SPECT was explored using two image process based on a Butterworth prefilter and post-filter: the original image processing (reconstruction A) with a cut-off frequency equals to 37% of the Nyquist frequency and order equals to 7, and a second image processing (reconstruction B) with a cut-off frequency equals to 25% of the Nyquist frequency and order equals to 5. For each patient, sum stress or rest score with and without septum (SSRS and SSRSws) were calculated with the two reconstructions. No significant statistical difference between SSRSa and SSRSb was identified for the first arm (P = 0.54) and the relative difference ∆r was − 0.5 ± 11.1% (95% CI − 2.7 to 1.7). We found a significant statistical difference between SSRSa and SSRSb for the second arm (p < 0.0001) and the relative difference ∆r was 69.7 ± 16.2% (95% CI 66.6–72.9).

Conclusion

In conclusion, using a Butterworth prefilter and post-filter cut-off frequency equal to 25% of the Nyquist frequency before iterative reconstruction generates less artefact and improves myocardial SPECT specificity without affecting sensibility compared with the original reconstruction.
Evaluation of the theranostic potential of [64Cu]CuCl2 in glioblastoma spheroids
Authors: Pinto Catarina I. G. , Branco André D. M. , Bucar Sara , Fonseca Alexandra , Abrunhosa Antero J. , da Silva Cláudia L. , Guerreiro Joana F. , Mendes Filipa
Published: March 2024

Background

Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS).

Results

Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu.

Conclusions

Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.
Caputo fractional backward stochastic differential equations driven by fractional Brownian motion with delayed generator
Authors: Shao Yunze , Du Junjie , Li Xiaofei , Tan Yuru , Song Jia
Published: March 2024

Over the years, the research of backward stochastic differential equations (BSDEs) has come a long way. As a extension of the BSDEs, the BSDEs with time delay have played a major role in the stochastic optimal control, financial risk, insurance management, pricing, and hedging. In this paper, we study a class of BSDEs with time-delay generators driven by Caputo fractional derivatives. In contrast to conventional BSDEs, in this class of equations, the generator is also affected by the past values of solutions. Under the Lipschitz condition and some new assumptions, we present a theorem on the existence and uniqueness of solutions.
Temporal and spatial distribution characteristics of the Ming Great Wall
Authors: Yang Yang , Zhang Yukun , Li Yan
Published: March 2024

The Great Wall during the Ming Dynasty (1368–1644) was the most prominent engineering volume and the most perfect military defense structure in the history of China. By combining traditional historical textual research, site surveys, and GIS database analysis, this paper reveals the Ming Great Wall’s spatial and temporal distribution characteristics and the immediate causes of their formation are discussed in the nine military districts of the frontier. The results show that: (1) The general rule of the Ming Great Wall was to set up military forts, passes, piers, and other related defensive facilities before constructing the continuous wall. (2) The Great Wall spatial and temporal distribution of the phases is relatively apparent, divided into five construction phases in the Ming Dynasty (1368–1620): Hongwu to Xuande (1368–1435), unbuilt the wall; Zhengtong to Tianshun (1436–1464), the consecutive wall appeared; Chenghua to Zhengde (1465–1521), the first construction climax of the Great Wall; Jiajing period (1522–1566), the second construction climax of the Great Wall; Longqing to Wanli (1567–1620), the completion of the whole line of the Great Wall.(3)The warfare and defense posture was the immediate factor that prompted the construction of the Great Wall between the Ming Dynasty and Mongolia. This study has some reference significance for restoring the integrity and authenticity of the Ming Great Wall, and contribute to the preservation of the cultural heritage of.
Comparative analysis of volatile fingerprints between different geographical origins and ornamental cultivars of white standard Chrysanthemum (Dendranthema grandiflorum)
Authors: Lee Ji Hye , An Jae Min , Kim Yong-Kyoung , Hur Suel Hye , Park Sang Un , Kim Ho Jin
Published: March 2024

Background

White standard Dendranthema grandiflorum (D. grandiflorum) is widely used for ornamental purposes. The volatile organic components (VOCs) of D. grandiflorum vary depending on the geographical origin and cultivar, which influence the market value. Here, we applied headspace extraction coupled with gas chromatography–mass spectrometry (HS–GC–MS) for the first time to determine the different origins (Korea, China, Vietnam) of D. grandiflorum in three genotypes (Baekgang, Jinba, Iwa-no-hakusen) based on volatile fingerprints and to assess the correlation among the metabolites identified in Korean and non-Korean D. grandiflorum.

Results

A total of 41 VOCs, mainly monoterpenoids, sesquiterpenoids, alcohols, and fatty acids, were identified. Principal component analysis showed that instead of geographical origin, genotype influences D. grandiflorum fingerprints. Cultivar discrimination was mainly affected by the metabolites associated with the alpha-terpinyl cation pathway. The orthogonal partial least squares discriminant analysis model achieved 100% and 93.3% accuracies in the calibration and validation sets, respectively. The results of volcano plots and clustering analysis, sesquiterpenoids were significantly more abundant in non-Korean than in Korean, whereas monoterpenoids were abundant in Korean samples.

Conclusions

41 makers confirmed robustness maintenance over two years. These findings can be useful for reliably identifying the geographical origin of D. grandiflorum and providing a comprehensive understanding of VOCs in D. grandiflorum cultivars grown in different countries of origins.

Graphical Abstract
Association of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use and Patient Outcomes in Advanced Non–Small-Cell Lung Cancer
Authors: Yorio Jeff , Lofgren Katherine T. , Lee Jessica K. , Tolba Khaled , Oxnard Geoffrey R. , Schrock Alexa B. , Huang Richard S.P. , Brisbin Lorraine
Published: March 2024

PURPOSE

Timely biomarker testing remains out of reach for many patients with advanced non–small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions.

METHODS

Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP results were available before or after 1L therapy initiation.

RESULTS

In total, 2,694 patients were included in the 1L therapy decision impact assessment. Timely CGP increased matched targeted therapy use by 14 percentage points (17% with CGP v 2.8% without) and precision immune checkpoint inhibitor (ICPI) use by 14 percentage points (18% with CGP v 3.9% without). Receipt of timely CGP resulted in an estimated 31 percentage point decrease in ICPI use among ALK/EGFR/RET/ROS1-positive patients at an expected per-patient reduction in ineffective ICPI therapy cost of $13,659.37 with timely CGP to inform 1L treatment selection. Patient benefit of CGP extended to real-world time to therapy discontinuation (median time to therapy discontinuation: 3.9 v 10 months [hazard ratio, HR, 0.54 [95% CI, 0.42 to 0.70]; P = 1.9E-06; adjusted hazard ratio [aHR], 0.50 [95% CI, 0.38 to 0.67]; P = 2.0E-06) in 1L driver-positive patients. This effect was not significant for real-world overall survival (median overall survival: 32 v 29 months [HR, 1.2 [95% CI, 0.84 to 1.67]; P = .33; aHR, 1.4 [95% CI, 0.92 to 1.99]; P = .12).

CONCLUSION

Timely CGP is associated with the quality of patient care as measured by 1L matched targeted therapy use, time to therapy discontinuation, and avoidance of ineffective, costly ICPIs.
“A Face of Anguish”: Pain and Portraiture in the Civil War Hospital
Authors: Libow Jess
Published: March 2024

This essay traces the visual cultures that emerged around Civil War soldiers’ pain and argues that the method of portraiture has much to offer the field of health humanities. It begins by tracing efforts to capture Civil War soldiers’ pain in both popular and clinical media before turning to hospital accounts by Louisa May Alcott and Walt Whitman that adopt the trope of portraiture in order to make soldiers’ suffering legible to a wider audience. This essay argues that these ekphrastic accounts make visible not only soldiers’ suffering but also the act of observing and interpreting it, and the essay concludes by suggesting that by bringing into focus the process of perceiving another’s pain, the study of portraiture offers an important complement to both the field of narrative medicine and health humanities approaches to studying visual art.