bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and clinical characteristics of Sarcopenia in older adult patients with stable chronic obstructive pulmonary disease: a cross-sectional and follow-up study
Authors: Kim Sang Hun , Hong Cho Hui , Shin Myung-Jun , Kim Ki Uk , Park Tae Sung , Park Jun Yong , Shin Yong Beom
Published: May 2024

Background

The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months.

Methods

In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered.

Results

At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase.

Conclusion

A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period.

Trial registration

The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.
F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/β-Catenin pathway
Authors: Li Zhengrui , Liu Yuan , Huang Xufeng , Wang Qi , Fu Rao , Wen Xutao , Liu Ji’an , Zhang Ling
Published: May 2024

Background

Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown.

Methods

In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments.

Results

Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention.

Conclusion

Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.
Survival estimation of oral cancer using fuzzy deep learning
Authors: Somyanonthanakul Rachasak , Warin Kritsasith , Chaowchuen Sitthi , Jinaporntham Suthin , Panichkitkosolkul Wararit , Suebnukarn Siriwan
Published: May 2024

Background

Oral cancer is a deadly disease and a major cause of morbidity and mortality worldwide. The purpose of this study was to develop a fuzzy deep learning (FDL)-based model to estimate the survival time based on clinicopathologic data of oral cancer.

Methods

Electronic medical records of 581 oral squamous cell carcinoma (OSCC) patients, treated with surgery with or without radiochemotherapy, were collected retrospectively from the Oral and Maxillofacial Surgery Clinic and the Regional Cancer Center from 2011 to 2019. The deep learning (DL) model was trained to classify survival time classes based on clinicopathologic data. Fuzzy logic was integrated into the DL model and trained to create FDL-based models to estimate the survival time classes.

Results

The performance of the models was evaluated on a test dataset. The performance of the DL and FDL models for estimation of survival time achieved an accuracy of 0.74 and 0.97 and an area under the receiver operating characteristic (AUC) curve of 0.84 to 1.00 and 1.00, respectively.

Conclusions

The integration of fuzzy logic into DL models could improve the accuracy to estimate survival time based on clinicopathologic data of oral cancer.
Understanding the value of a doctorate for allied health professionals in practice in the UK: a survey
Authors: Watson Jo , Robertson Steven , Ryan Tony , Wood Emily , Cooke Jo , Hampshaw Susan , Roddam Hazel
Published: May 2024

Background

The need to transform the United Kingdom’s (UK) delivery of health and care services to better meet population needs and expectations is well-established, as is the critical importance of research and innovation to drive those transformations. Allied health professionals (AHPs) represent a significant proportion of the healthcare workforce. Developing and expanding their skills and capabilities is fundamental to delivering new ways of working. However, career opportunities combining research and practice remain limited. This study explored the perceived utility and value of a doctorate to post-doctoral AHPs and how they experience bringing their research-related capabilities into practice environments.

Methods

With a broadly interpretivist design, a qualitatively oriented cross-sectional survey, with closed and open questions, was developed to enable frequency reporting while focusing on the significance and meaning participants attributed to the topic. Participants were recruited via professional networks and communities of practice. Descriptive statistics were used to analyse closed question responses, while combined framework and thematic analysis was applied to open question responses.

Results

Responses were received from 71 post-doctoral AHPs located across all four UK nations. Findings are discussed under four primary themes of utilisation of the doctorate; value of the doctorate; impact on career, and impact on self and support. Reference is also made at appropriate points to descriptive statistics summarising closed question responses.

Conclusion

The findings clearly articulate variability of experiences amongst post-doctoral AHPs. Some were able to influence team and organisational research cultures, support the development of others and drive service improvement. The challenges, barriers and obstacles encountered by others reflect those that have been acknowledged for many years. Acknowledging them is important, but the conversation must move forward and generate positive action to ensure greater consistency in harnessing the benefits and value-added these practitioners bring. If system-wide transformation is the aim, it is inefficient to leave navigating challenges to individual creativity and tenacity or forward-thinking leaders and organisations. There is an urgent need for system-wide responses to more effectively, consistently and equitably enable career pathways combining research and practice for what is a substantial proportion of the UK healthcare workforce.
No genetic causal association between periodontitis and ankylosing spondylitis: a bidirectional two-sample mendelian randomization analysis
Authors: Han Chong , Wu Dongchao , Yu Feiyan , Wang Qianqian , Yang Yang , Li Yi , Qin Rao , Chen Yue , Xu Linkun , He Dongning
Published: May 2024

Background

Observational studies that reveal an association between periodontitis (PD) and ankylosing spondylitis (AS) exist. However, observational research is prone to reverse causality and confounding factors, which make it challenging to infer cause-and-effect relationships. We conducted a two-sample Mendelian randomization (MR) study to examine the causal relationship between the genetic prediction of PD and AS.

Methods

In our study, single-nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs). The genetic association with PD came from the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) consortium, wherein 17353 cases of European ancestry and 28210 controls of European ancestry were included in this study. The genetic association with AS from the Neale Laboratory Consortium included 337,159 individuals from the United Kingdom, with 968 cases and 336,191 controls. MR analysis was mainly performed using the inverse-variance weighted (IVW) method. In addition, the robustness of the study findings was assessed using sensitivity, pleiotropy, and heterogeneity analyses.

Results

Eighteen independent SNPs with P-values significantly smaller than 1 × 10− 5 were used as IV SNPs for PD, while 39 independent SNPs with P-values significantly smaller than 1 × 10− 5 were used as IV SNPs for AS. The results of the IVW method revealed no causal association between PD and AS (odds ratio = 1.00, 95% confidence interval: 0.99953 to 1.00067, P = 0.72). The MR-Egger method did not support the causal association between PD and AS. It is unlikely that horizontal pleiotropy distorts causal estimates based on sensitivity analysis. No significant heterogeneity was observed in the Q test. The ‘’leave-one-out’’ analysis demonstrated that the robustness of our results was unaffected by eliminating any of the IVs. Likewise, no significant causative effect for AS on PD was observed in the inverse MR analysis.

Conclusions

The study results do not support shared heritability or a causal association between PD and AS.
Examining global Indigenous community wellness worker models: a rapid review
Authors: Fitzpatrick Kayla M. , Sjoblom Erynne , Puinean Giulia , Robson Heath , Campbell Sandra M. , Fayant Bryan , Montesanti Stephanie
Published: May 2024

Background

There is a growing interest in employing community wellness worker models in Indigenous populations to address inequities in healthcare access and outcomes, concerns about shortage in health and mental health human resources, and escalating burden of chronic and complex diseases driving significant increase in health services demand and costs. A thorough review of Indigenous community wellness worker models has yet to be conducted. This rapid review sought to outline the characteristics of a community wellness worker model in Indigenous contexts across the globe, detailing factors shaping implementation challenges and success.

Methods

A rapid review of the international peer-reviewed and grey literature of OVID Medline, Global Index Medicus, Google, and Google Scholar was conducted from January to June 2022 for Indigenous community wellness/mental health worker models and comparative models. Articles were screened and assessed for eligibility. From eligible articles, data pertaining to study design and sample; description of the program, service, or intervention; model development and implementation; terminology used to describe workers; training features; job roles; funding considerations; facilitators and barriers to success; key findings; outcomes measured; and models or frameworks utilized were extracted. Data were synthesized by descriptive and pattern coding.

Results

Twenty academic and eight grey literature articles were examined. Our findings resulted in four overarching and interconnected themes: (1) worker roles and responsibilities; (2) worker training, education, and experience; (3) decolonized approaches; and (4) structural supports.

Conclusion

Community wellness worker models present a promising means to begin to address the disproportionately elevated demand for mental wellness support in Indigenous communities worldwide. This model of care acts as a critical link between Indigenous communities and mainstream health and social service providers and workers fulfill distinctive roles in delivering heightened mental wellness supports to community members by leveraging strong ties to community and knowledge of Indigenous culture. They employ innovative structural solutions to bolster their efficacy and cultivate positive outcomes for service delivery and mental wellness. Barriers to the success of community wellness worker models endure, including power imbalances, lack of role clarity, lack of recognition, mental wellness needs of workers and Indigenous communities, and more.
Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy
Authors: Sukocheva Olga A. , Neganova Margarita E. , Aleksandrova Yulia , Burcher Jack T. , Chugunova Elena , Fan Ruitai , Tse Edmund , Sethi Gautam , Bishayee Anupam , Liu Junqi
Published: May 2024

Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.
An algorithm to identify patients aged 0–3 with rare genetic disorders
Authors: Webb Bryn D. , Lau Lisa Y. , Tsevdos Despina , Shewcraft Ryan A. , Corrigan David , Shi Lisong , Lee Seungwoo , Tyler Jonathan , Li Shilong , Wang Zichen , Stolovitzky Gustavo , Edelmann Lisa , Chen Rong , Schadt Eric E. , Li Li
Published: May 2024

Background

With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured electronic medical record data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders. We sought to develop a digital phenotyping algorithm (PheIndex) using electronic medical records to identify children aged 0–3 diagnosed with genetic disorders or who present with illness with an increased risk for genetic disorders.

Results

Through expert opinion, we established 13 criteria for the algorithm and derived a score and a classification. The performance of each criterion and the classification were validated by chart review. PheIndex identified 1,088 children out of 93,154 live births who may be at an increased risk for genetic disorders. Chart review demonstrated that the algorithm achieved 90% sensitivity, 97% specificity, and 94% accuracy.

Conclusions

The PheIndex algorithm can help identify when a rare genetic disorder may be present, alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist.
Colorectal carcinoma peritoneal metastases-derived organoids: results and perspective of a model for tailoring hyperthermic intraperitoneal chemotherapy from bench-to-bedside
Authors: Varinelli Luca , Battistessa Davide , Guaglio Marcello , Zanutto Susanna , Illescas Oscar , Lorenc Ewelina J. , Pisati Federica , Kusamura Shigeki , Cattaneo Laura , Sabella Giovanna , Milione Massimo , Perbellini Alessia , Noci Sara , Paolino Cinzia , Kuhn Elisabetta , Galassi Margherita , Cavalleri Tommaso , Deraco Marcello , Gariboldi Manuela , Baratti Dario
Published: May 2024

Background

Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy.

Methods

Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage.

Results

Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity.

Conclusions

Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.
Information needs of Lynch syndrome and BRCA 1/2 mutation carriers considering risk-reducing gynecological surgery: a qualitative study of the decision-making process
Authors: Zhao Lucy , Lynch Lorrie , Eiriksson Lua
Published: May 2024

Background

Risk-reducing gynecological surgery (RRGS) is a prophylactic procedure that may be offered to BRCA1, BRCA2, and Lynch syndrome (LS) mutation carriers to reduce the risk of developing gynecological cancer. This study was conducted to better understand patients’ information needs and evaluate how patients weigh different sources of information in their decision-making process surrounding RRGS.

Methods

This study used a qualitative approach to understanding women’s perspectives towards RRGS. Semi-structured interviews were conducted virtually with 8 women. Women offered RRGS between 35 and 70 years of age who are English-speaking and have an identifiable BRCA or LS mutation were included. Data from interviews was coded with constant comparative analysis to develop themes.

Results

Of the eight women, six had selected to undergo either prophylactic hysterectomy or oophorectomy: 5 decided yes to RRGS; 1 decided no; 2 were undecided. Thematic analysis found that the key factors affecting women’s decisions around prophylactic surgery were cancer risk, surgical menopause, and psychological readiness. To make an informed decision, women relied most heavily on information provided by healthcare professionals (e.g. doctors, genetic counselors) and family members with prior cancer experience. However, some women reported that they did not feel adequately informed enough to make a decision and identified COVID-19 as a significant barrier affecting access to information.

Conclusion

This qualitative study revealed the key sources of information influencing attitudes regarding RRGS and how women consulted different sources of information to reach a decision. Results underscore the need for greater attention to women’s information needs in the context of psychological readiness, particularly amidst the pandemic. Research involving a larger sample size may help to better inform how support can be provided to individuals with BRCA and LS mutations considering RRGS.
Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial)
Authors: Inbaraj Leeberk Raja , Manesh Abi , Ponnuraja C. , Bhaskar Adhin , Srinivasalu Vignes Anand , Daniel Bella Devaleenal
Published: May 2024

Background

Despite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM.

Methods

An open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. 

Discussion

Current WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM.

Trial registration

Clinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340).

Protocol version

Version 1.3 dated 12 July 2023.
Capitella teleta gets left out: possible evolutionary shift causes loss of left tissues rather than increased neural tissue from dominant-negative BMPR1
Authors: Webster Nicole B. , Meyer Néva P.
Published: May 2024

Background

The evolution of central nervous systems (CNSs) is a fascinating and complex topic; further work is needed to understand the genetic and developmental homology between organisms with a CNS. Research into a limited number of species suggests that CNSs may be homologous across Bilateria. This hypothesis is based in part on similar functions of BMP signaling in establishing fates along the dorsal-ventral (D-V) axis, including limiting neural specification to one ectodermal region. From an evolutionary-developmental perspective, the best way to understand a system is to explore it in a wide range of organisms to create a full picture.

Methods

Here, we expand our understanding of BMP signaling in Spiralia, the third major clade of bilaterians, by examining phenotypes after expression of a dominant-negative BMP Receptor 1 and after knock-down of the putative BMP antagonist Chordin-like using CRISPR/Cas9 gene editing in the annelid Capitella teleta (Pleistoannelida).

Results

Ectopic expression of the dominant-negative Ct-BMPR1 did not increase CNS tissue or alter overall D-V axis formation in the trunk. Instead, we observed a unique asymmetrical phenotype: a distinct loss of left tissues, including the left eye, brain, foregut, and trunk mesoderm. Adding ectopic BMP4 early during cleavage stages reversed the dominant-negative Ct-BMPR1 phenotype, leading to a similar loss or reduction of right tissues instead. Surprisingly, a similar asymmetrical loss of left tissues was evident from CRISPR knock-down of Ct-Chordin-like but concentrated in the trunk rather than the episphere.

Conclusions

Our data highlight a novel asymmetrical phenotype, giving us further insight into the complicated story of BMP’s developmental role. We further solidify the hypothesis that the function of BMP signaling during the establishment of the D-V axis and CNS is fundamentally different in at least Pleistoannelida, possibly in Spiralia, and is not required for nervous system delimitation in this group.
Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth
Authors: Corbett Blythe A. , Muscatello Rachael A. , McGonigle Trey , Vandekar Simon , Burroughs Christina , Sparks Sloane
Published: May 2024

Background

Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course.

Method

The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females).

Results

Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development.

Limitations

Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic.

Conclusions

Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.
Metastasis of small cell lung cancer to bilateral extraocular muscles: a case report
Authors: Ramalhão João Ponces , Vieira Beatriz Costa , Rodrigues Diogo , Afonso Miguel Gonçalves , Gouveia João , Baptista Pedro Manuel , Araújo Maria
Published: May 2024

Background

Orbital metastasis is a possible complication of small cell lung cancer and a pattern of bilateral invasion of the extraocular muscles has rarely been reported in literature.

Case presentation

A 46-year-old white male with a past medical history of smoking and stage IV small cell lung carcinoma presented with loss of vision and pain in the left eye. Examination revealed bilateral proptosis and left afferent pupillary defect, and visual acuity was hand motion on the left eye and 4/10 on the right eye. An orbital computed tomography scan showed a compression of the left optic nerve between the extraocular muscles at the apex, and a lateral canthotomy was performed for a new-onset compressive optic neuropathy, with residual visual improvement. There was also significant enlargement of the extraocular muscles in the right orbit. The patient was maintained in palliative treatment with both chemotherapy and local medical and surgical (amniotic membrane cover for exposure keratopathy) ophthalmological treatments until he eventually died 5 months after.

Conclusion

Bilateral metastasis to the extraocular muscles is a very rare manifestation of small cell lung cancer and the palliative treatment in these cases is challenging.
Melanotic neuroectodermal tumor of infancy: a case report
Authors: Asefa Mesfin , Hailu Tedros
Published: May 2024

Background

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare clinically benign, pigmented, tumor of neural crest origin which commonly occurs in the maxilla. It is a rare tumor that may pose difficulty in differentiating from other malignant round cell tumors.

Case presentation

A 5-month-old Ethiopian infant presented with a mass on his forehead. A wide excision of the lesion was done and subjected to histopathologic evaluation. The histologic and immunohistochemistry for synaptophysin studies confirmed that the infant was having MNTI. The patient was followed and there was no sign of recurrence at the 6th and 9th months of follow-up.

Conclusion

MNTI should be considered as a differential diagnosis for tumors occurring in the head region in infants and prolonged follow-up may be needed to check for possible recurrence of the tumor.
The history of palaeontological research and excavations at Monte San Giorgio
Authors: Furrer Heinz
Published: May 2024

There is a long history of palaeontological excavations at Monte San Giorgio (Switzerland) and the adjoining Monte Pravello—Monte Orsa (Italy), aimed at finding well-preserved skeletons of Middle Triassic vertebrates. The first fossils were discovered in the mid-Nineteenth Century during mining of black shales (scisti bituminosi) near Besano, Italy, with further finds in the early Twentieth Century through industrial-scale mining. Studies of the material generated international interest and prompted formal palaeontological excavations on both sides of the border. The earliest excavations took place in 1863 and 1878, with the most extensive between 1924 and 1968. Systematic excavations have continued up to the present day, focusing on six distinct fossiliferous horizons: the Besano Formation and the overlying Meride Limestone with the Cava inferiore, Cava superiore, Cassina, Sceltrich and Kalkschieferzone beds. All these have provided material for study and display, with Monte San Giorgio itself recently designated a UNESCO World Heritage Site. The workers and organisations involved, locations excavated and material recovered are described herein.
Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study
Authors: Wozniak Hannah , Tabah Alexis , Barbier François , Ruckly Stéphane , Loiodice Ambre , Akova Murat , Leone Marc , Conway Morris Andrew , Bassetti Matteo , Arvaniti Kostoula , Ferrer Ricard , de Bus Liesbet , Paiva Jose Artur , Bracht Hendrik , Mikstacki Adam , Alsisi Adel , Valeanu Liana , Prazak Josef , Timsit Jean-François , Buetti Niccolò ,   on behalf of the EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and the OUTCOMEREA Network
Published: May 2024

Background

Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality.

Methods

Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model.

Results

Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3–4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01–1.7, p = 0.045).

Conclusions

Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.
Comparative analysis of Cochrane and non-Cochrane reviews over three decades
Authors: Andersen Mikkel Zola , Zeinert Philine , Rosenberg Jacob , Fonnes Siv
Published: May 2024

Background

Systematic reviews are viewed as the best study design to guide clinical decision-making as they are the least biased publications assuming they are well-conducted and include well-designed studies. Cochrane was initiated in 1993 with an aim of conducting high-quality systematic reviews. We aimed to examine the publication rates of non-Cochrane systematic reviews (henceforth referred to simply as “systematic reviews”) and Cochrane reviews produced throughout Cochrane’s existence and characterize changes throughout the period.

Methods

This observational study collected data on systematic reviews published between 1993 and 2022 in PubMed. Identified Cochrane reviews were linked to data from the Cochrane Database of Systematic Reviews via their Digital Object Identifier. Systematic reviews and Cochrane reviews were analyzed separately. Two authors screened a random sample of records to validate the overall sample, providing a precision of 98%.

Results

We identified 231,602 (94%) systematic reviews and 15,038 (6%) Cochrane reviews. Publication of systematic reviews has continuously increased with a median yearly increase rate of 26%, while publication of Cochrane reviews has decreased since 2015. From 1993 to 2002, Cochrane reviews constituted 35% of all systematic reviews in PubMed compared with 3.5% in 2013–2022. Systematic reviews consistently had fewer authors than Cochrane reviews, but the number of authors increased over time for both. Chinese first authors conducted 15% and 4% of systematic reviews published from 2013–2022 and 2003–2012, respectively. Most Cochrane reviews had first authors from the UK (36%). The native English-speaking countries the USA, the UK, Canada, and Australia produced a large share of systematic reviews (42%) and Cochrane reviews (62%). The largest publishers of systematic reviews in the last 10 years were gold open access journals.

Conclusions

Publication of systematic reviews is increasing rapidly, while fewer Cochrane reviews have been published through the last decade. Native English-speaking countries produced a large proportion of both types of systematic reviews. Gold open access journals and Chinese first authors dominated the publication of systematic reviews for the past 10 years. More research is warranted examining why fewer Cochrane reviews are being published. Additionally, examining these systematic reviews for research waste metrics may provide a clearer picture of their utility.
The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells
Authors: Badr Omar I. , Kamal Mohamed M. , El-Maraghy Shohda A. , Ghaiad Heba R.
Published: May 2024

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals.

Results

Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups.

Conclusion

Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs.

Graphical Abstract
Anterior Cruciate Ligament Return to Sport after Injury Scale (ACL-RSI) Scores over Time After Anterior Cruciate Ligament Reconstruction: A Systematic Review with Meta-analysis
Authors: Sell Timothy C. , Zerega Ryan , King Victoria , Reiter Charles R. , Wrona Hailey , Bullock Garrett S. , Mills Nilani , Räisänen Anu , Ledbetter Leila , Collins Gary S. , Kvist Joanna , Filbay Stephanie R. , Losciale Justin M.
Published: May 2024

Background

Psychological readiness is an important consideration for athletes and clinicians when making return to sport decisions following anterior cruciate ligament reconstruction (ACLR). To improve our understanding of the extent of deficits in psychological readiness, a systematic review is necessary.

Objective

To investigate psychological readiness (measured via the Anterior Cruciate Ligament-Return to Sport after Injury scale (ACL-RSI)) over time after ACL tear and understand if time between injury and surgery, age, and sex are associated with ACL-RSI scores.

Methods

Seven databases were searched from the earliest date available to March 22, 2022. Articles reporting ACL-RSI scores after ACL tear were included. Risk of bias was assessed using the ROBINS-I, RoB-2, and RoBANS tools based on the study design. Evidence certainty was assessed for each analysis. Random-effects meta-analyses pooled ACL-RSI scores, stratified by time post-injury and based on treatment approach (i.e., early ACLR, delayed ACLR, and unclear approach).

Results

A total of 83 studies were included in this review (78% high risk of bias). Evidence certainty was ‘weak’ or ‘limited’ for all analyses. Overall, ACL-RSI scores were higher at 3 to 6 months post-ACLR (mean = 61.5 [95% confidence interval (CI) 58.6, 64.4], I2 = 94%) compared to pre-ACLR (mean = 44.4 [95% CI 38.2, 50.7], I2 = 98%), remained relatively stable, until they reached the highest point 2 to 5 years after ACLR (mean = 70.7 [95% CI 63.0, 78.5], I2 = 98%). Meta-regression suggests shorter time from injury to surgery, male sex, and older age were associated with higher ACL-RSI scores only 3 to 6 months post-ACLR (heterogeneity explained R2 = 47.6%), and this reduced 1–2 years after ACLR (heterogeneity explained R2 = 27.0%).

Conclusion

Psychological readiness to return to sport appears to improve early after ACL injury, with little subsequent improvement until ≥ 2-years after ACLR. Longer time from injury to surgery, female sex and older age might be negatively related to ACL-RSI scores 12–24 months after ACLR. Due to the weak evidence quality rating and the considerable importance of psychological readiness for long-term outcomes after ACL injury, there is an urgent need for well-designed studies that maximize internal validity and identify additional prognostic factors for psychological readiness at times critical for return to sport decisions.

Registration: Open Science Framework (OSF), https://osf.io/2tezs/.
Quantitative Analysis of 92 12-Week Sub-elite Marathon Training Plans
Authors: Knopp Melanie , Appelhans Daniel , Schönfelder Martin , Seiler Stephen , Wackerhage Henning
Published: May 2024

Background

A typical training plan is a mix of many training sessions with different intensities and durations to achieve a specific goal, like running a marathon in a certain time. Scientific publications provide little specific information to aid in writing a comprehensive training plan. This review aims to systematically and quantitatively analyse the last 12 weeks before a marathon as recommended in 92 sub-elite training plans.

Methods

We retrieved 92 marathon training plans and linked their running training sessions to five intensity zones. Subsequently, each training plan was grouped based on the total running volume in peak week into high (> 90 km/week), middle (65–90 km/week), and low (< 65 km/week) training volume plan categories.

Results

In the final 12 weeks before a race, recommended weekly running volume averaged 108 km, 59 km, and 43 km for high, middle, and low distance marathon training plans. The intensity distribution of these plans followed a pyramidal training structure with 15–67–10–5–3%, 14–63–18–2–3%, and 12–67–17–2–2% in zones 1, 2, 3, 4, and 5, for high, middle, and low volume training plans, respectively.

Conclusions

By quantitatively analysing 92 recommended marathon training plans, we can specify typical recommendations for the last 12 weeks before a marathon race. Whilst this approach has obvious limitations such as no evidence for the effectiveness of the training plans investigated, it is arguably a useful strategy to narrow the gap between science and practice.
99mTc-labeled FAPI compounds for cancer and inflammation: from radiochemistry to the first clinical applications
Authors: Boschi Alessandra , Urso Luca , Uccelli Licia , Martini Petra , Filippi Luca
Published: May 2024

Background

In recent years, fibroblast activating protein (FAP), a biomarker overexpressed by cancer-associated fibroblasts, has emerged as one of the most promising biomarkers in oncology. Similarly, FAP overexpression has been detected in various fibroblast-mediated inflammatory conditions such as liver cirrhosis and idiopathic pulmonary fibrosis. Along this trajectory, FAP-targeted positron emission tomography (PET), utilizing FAP inhibitors (FAPi) labeled with positron emitters, has gained traction as a powerful imaging approach in both cancer and inflammation. However, PET represents a high-cost technology, and its widespread adoption is still limited compared to the availability of gamma cameras. To address this issue, several efforts have been made to explore the potential of [99mTc]Tc-FAPi tracers as molecular probes for imaging with gamma cameras and single photon emission computed tomography (SPECT).

Main body

Several approaches have been investigated for labeling FAPi-based compounds with 99mTc. Specifically, the mono-oxo, tricarbonyl, isonitrile, and HYNIC strategies have been applied to produce [99mTc]Tc-FAPi tracers, which have been tested in vitro and in animal models. Overall, these labeling approaches have demonstrated high efficiency and strong binding. The resulting [99mTc]Tc-FAPi tracers have shown high specificity for FAP-positive cells and xenografts in both in vitro and animal model studies, respectively. However, the majority of [99mTc]Tc-FAPi tracers have exhibited variable levels of lipophilicity, leading to preferential excretion through the hepatobiliary route and undesirable binding to lipoproteins. Consequently, efforts have been made to synthesize more hydrophilic FAPi-based compounds to improve pharmacokinetic properties and achieve a more favorable biodistribution, particularly in the abdominal region. SPECT imaging with [99mTc]Tc-FAPi has yielded promising results in patients with gastrointestinal tumors, demonstrating comparable or superior diagnostic performance compared to other imaging modalities. Similarly, encouraging outcomes have been observed in subjects with gliomas, lung cancer, breast cancer, and cervical cancer. Beyond oncological applications, [99mTc]Tc-FAPi-based imaging has been successfully employed in myocardial and idiopathic pulmonary fibrosis.

Conclusions

This overview focuses on the various radiochemical strategies for obtaining [99mTc]Tc-FAPi tracers, highlighting the main challenges encountered and possible solutions when applying each distinct approach. Additionally, it covers the preclinical and initial clinical applications of [99mTc]Tc-FAPi in cancer and inflammation.