bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Status and End-of-Life Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Androgen Receptor Targeted Therapy
Authors: Mellgard George , Saffran Nathaniel , Chakrani Zakaria , McCroskery Stephen , Taylor Nicole , Patel Mann , Liaw Bobby , Galsky Matthew , Oh William , Tsao Che-Kai , Patel Vaibhav
Published: August 2024

Objectives:

Androgen receptor targeted therapies (ARTs) are widely preferred over taxane chemotherapy due to their good tolerability and similar efficacy. However, there is a paucity of data that support the use of ART therapy or describe end-of-life (EOL) outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) with reduced performance status (PS) (European Cooperative Oncology Group [ECOG] ≥2).

Methods:

We performed a retrospective, single-institution study of 142 patients with mCRPC who received ART therapy between 2010 and 2021. We assessed each record for baseline demographic and clinical information, ART treatment course, and survival and EOL outcomes. Our primary aim was to compare overall survival (OS) between the two groups (ECOG ≥2 vs 0 to 1), and our secondary aim was to describe EOL outcomes. Fisher exact tests and Wilcoxon signed-rank tests were used to compare baseline characteristics. Cox regression was used to compare OS for patients with ECOG ≥2 at the start of treatment with those who had an ECOG of 0 or 1. Descriptive analyses were performed to assess EOL outcomes between the groups.

Results:

Patients with mCRPC and decreased PS experienced shorter OS on ART compared with those with higher PS. Moreover, when examining EOL outcomes, a near majority of these patients died in the hospital, with a greater percentage among those with an ECOG ≥2.

Conclusion:

These findings highlight the need for continual assessment of PS, improved shared decision-making in ART treatment, and additional research exploring the association between PS and EOL outcomes.
Ten Myths in Nerve Surgery
Authors: Duraku Liron S. , Eberlin Kyle R. , Moore Amy , Lu Johnny , Chaudhry Tahseen , George Samuel , Burahee Abdus S. , Zuidam J. Michiel , Bertelli Jayme , Power Dominic M.
Published: August 2024

Background:

Surgical innovation has provided new options for the management of complex peripheral nerve injuries, generating renewed interest in this field. Historic literature may be misinterpreted or misquoted, or create dogma, which is perpetuated in teaching, research publications, and clinical practice. The management of peripheral nerve injuries is based on complex decision-making, with potential lifelong ramifications for patients incorrectly receiving an expectant or surgical management plan.

Methods:

This article includes opinion from expert leaders in the field of peripheral nerve surgery and questions some of the current assumptions and preconceptions around nerve surgery based on clinical evidence. There was extensive debate regarding the contents of the final article, and the different opinions expressed represent the uncertainty in this field and the differing levels of confidence in available published evidence.

Results:

Individual practices vary and, therefore, absolute consensus is impossible to achieve. The work is presented as 10 myths which are assessed using both historical and emerging evidence, and areas of uncertainty are discussed.

Conclusions:

It is important to learn lessons from the past, and scholars of history bear the task of ensuring references are accurately quoted. Expunging myths will enhance care for patients, focus research efforts, and expand on the surgical possibilities within this specialty.
A Simple and Effective Approach to Defatting Large Surface Area Full-thickness Skin Grafts
Authors: Roblee Cole V. , Mankowski Peter , Marquette Lauren , Gast Katherine M. , Kuzon William M.
Published: August 2024

Skin grafting is a fundamental tool in plastic surgery for the resurfacing of wounds resulting from burns, necrotizing infections, trauma, oncologic resections, donor site defects, and other causes. Compared with split-thickness skin grafts, full-thickness skin grafts (FTSGs) undergo less secondary contracture and often result in better aesthetic outcomes. To assure graft take, FTSGs require thorough defatting and adequate contact between the graft and the underlying wound bed. Conventionally, during the defatting process, FTSGs are stabilized on the surgeon’s fingers, whereas curved scissors are used to remove the subcutaneous tissue. This approach is effective for small grafts, but for large FTSGs, it is time-consuming and ergonomically challenging.
A Longitudinal Evaluation of Collaboration in Plastic Surgery Clinical Research
Authors: Ewing Jane N. , Lemdani Mehdi S. , Gala Zachary , Amro Chris , Broach Robyn B. , Serletti Joseph , Fischer John P.
Published: August 2024

Background:

Few dedicated, funded clinical research fellowship positions exist in plastic surgery. This study provides insights from an established clinical research fellowship, highlighting its educational impact and confirming the impact of positive institutional support and a collaborative-first approach.

Methods:

All research fellows within the program from 2008 to 2020 were examined during their year of employment and subsequent 2 years. Internal and external collaboration trends were assessed using PubMed affiliations. Correlation between external collaborations and research impact were examined. Research impact was characterized by publication count, journal impact factor, and journal diversity.

Results:

Thirty-one research fellows were identified, with a 100% match rate. Four phases of development were identified, and a three-period cycle of productivity was noted to occur every 3 years. A shift toward more external collaborations occurred after 2016 (P = 0.008). A positive correlation was observed between external collaborations and academic output (r = 0.72, P = 0.004), journal diversity (r = 0.74, P = 0.004), and journal impact (r = 0.63, P < 0.05). Significant growth was observed in the collaborative networks (P = 0.002), publications (P = 0.003), journal diversity (P < 0.001), and research personnel (P = 0.002).

Conclusions:

As a result of our strategic decision to engage collaborators across multiple disciplines, there is discernible improvement in measurable impact, contributing to the growth of our program. Dedicating resources to foster deeper collaborations can enrich the field of plastic surgery research, recognizing that this investment fuels the cycle of productivity, offering promising returns to the future.
Intraocular Pressure Response to Perceived Stress in Juvenile-Onset Open Angle Glaucoma
Authors: Abokyi Samuel , Mordi Prince , Ntodie Michael , Ayobi Benedict , Kwasi Abu Emmanuel
Published: August 2024

Précis:

High perceived stress from academic pressure is associated with intraocular pressure (IOP) elevation and reduced fluctuation in juvenile-onset open angle glaucoma patients. Personalized stress assessment and relief strategies may serve as an adjunct therapy in glaucoma.

Objective:

To evaluate the effect of higher perceived stress, resulting from academic pressure, on IOP in juvenile-onset open angle glaucoma (JOAG) patients compared with healthy individuals.

Methods:

The study included 48 university students aged 18–27 years, comprising 24 JOAG patients on antiglaucoma eyedrops and 24 healthy controls. In an examiner-blind pretest-posttest design, participants’ IOP was measured weekly using Goldmann tonometry during three follow-up visits at the beginning and end of the academic semester. Perceived Stress Scale (PSS) scores were also evaluated at these 2-time points to capture the contrast in perceived stress between periods of low and high academic pressure.

Results:

The baseline PSS score at the semester’s start was lower in both groups (14.1±1.9 in glaucoma vs. 13.5±2.4 in control) and significantly increased by the end of the semester (29.2±2.1 vs. 28.5±1.3; P<0.001), indicating increased perceived stress. Concurrently, IOP rose from 22.01±5.87 to 25.08±5.84 mm Hg in the glaucoma group and from 11.36±2.03 to 13.65±2.11 mm Hg in the control group. Factorial analysis revealed a significant interaction between stress and JOAG (F
(1,94)=15.94, P=0.001), partial η2=0.08, with stress having a greater increase on IOP in the glaucoma group (+3.10 mm Hg) compared with the control group (+2.23 mm Hg) (t
(94)=4.457, P<0.001).

Conclusions:

Higher perceived stress significantly increases IOP, especially in JOAG patients, suggesting personalized stress management as a potential adjunct therapy for patients.
Femoroacetabular Impingement and Groin Injuries Among Soccer Players
Authors: Nickerson Morgan , Herickhoff Paul
Published: August 2024

Groin injuries and femoroacetabular impingement are common among soccer players and can provide a challenge in diagnosis, as well as treatment. Nonoperative and operative measures are the 2 predominant treatments. This current review investigates the recent literature on groin and femoroacetabular impingement injuries in soccer players, as well as potential treatment modalities.
Epidemiologic changes in thyroid disease
Authors: Acosta Gonzalo J. , Singh Ospina Naykky , Brito Juan P.
Published: August 2024

Purpose of review

To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities.

Recent findings

Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves’ disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease.

Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.
The Contribution of 68Ga-FAPI-04 PET/CT to Staging and Prognosis in Gastric Cancer
Authors: Beyhan Ediz , Çermik Tevfik Fikret , Erol Fenercioğlu Özge , Şahin Rahime , Alçin Göksel , Aksoy Tamer , Arslan Esra , Ergül Nurhan
Published: August 2024

Aim

This study aimed to compare the diagnostic capabilities of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT imaging in staging gastric carcinoma, exploring the impact of 68Ga-FAPI-04 PET/CT on treatment planning and its prognostic significance.

Methods

The research included 31 patients undergoing staging for gastric cancer, who received both 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT scans. We compared the SUVmax and SUVmean of the primary tumor and lymph nodes, the count of organ metastases, tumor-to-background ratios, and overall staging accuracy. Additionally, the study evaluated radiological progression-free survival and overall survival rates.

Results

The 68Ga-FAPI-04 PET/CT demonstrated superior efficacy in identifying the primary tumor compared with 18F-FDG PET/CT, particularly in cases of poorly cohesive, signet-ring cell, and mucinous subtypes, with detection rates of 96.7% versus 77.4% (P = 0.006 and P = 0.008, respectively). Analysis of lymph nodes showed a significantly higher detection of positive nodes with 68Ga-FAPI-04 (P = 0.026), although no significant differences were observed in SUVmax and tumor-to-background ratio on a patient basis (P > 0.05). SUVmax and tumor-to-background ratios for peritoneal involvement were notably higher with 68Ga-FAPI-04 PET/CT compared with 18F-FDG PET/CT (P = 0.04 for both). No significant differences were found in the detection of organ metastases and disease stage between the 2 imaging modalities (P > 0.05). Primary tumor uptake did not significantly impact radiological progression-free survival or overall survival in either modality.

Conclusions

68Ga-FAPI-04 PET/CT imaging surpasses 18F-FDG PET/CT in detecting the primary tumor, especially in poorly cohesive and signet-ring cell gastric cancer types, and offers improved accuracy in disease staging. This indicates its potential to enhance treatment management and prognostic assessment in gastric cancer patients.
The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs
Authors: Bénard-Séguin Étienne , Nielsen Christopher , Sarhan Abdullah , Al-Ani Abdullah , Sylvestre-Bouchard Antoine , Waldner Derek M. , De Lott Lindsey B. , Subramaniam Suresh , Costello Fiona ,   on behalf of COIL (Calgary Ophthalmology Innovation Laboratory)
Published: August 2024

Background:

Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody–associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON.

Methods:

This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set.

Results:

The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72–0.92). The model attained an accuracy of 76.2% (95% CI, 68.4–83.1), a sensitivity of 74.2% (95% CI, 55.9–87.4) and a specificity of 76.9% (95% CI, 67.6–85.0) in classifying images as non-MS–related ON.

Conclusions:

This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.
Estimating the Preferred Walking Speeds Based on the Center of Mass Work Analysis
Authors: Hosseini-Yazdi Seyed-Saleh , Bertram John EA
Published: August 2024

This study investigates the role of optimal push-off impulses in minimizing the total mechanical work dissipation per step, aiming to achieve passive single support work performance for a variety of walking conditions. By optimizing push-offs to cover the entire step’s energy demands, the single support work may become only storage and release of mechanical energy through tendons and tissues. Our simulations indicate that for each walking speed, there is an optimal push-off impulse that ensures energy balance without the need for additional energy input or dissipation during the subsequent single support phase when the soft tissue dissipation is negligible. For this circumstance, the step total dissipation is minimum. For level ground (even terrain), the estimated preferred walking speeds align closely with literature values for young adult (∼ 1.2 m.s−1)and older adult (∼ 1.0 m.s−1) self-selected speeds, with a reduction observed for the restricted view of oncoming irregularities in the substrate terrain (15%). For walking on uneven surfaces, terrain amplitude was shown to impact walking costs quadratically, with optimal speeds declining by approximately 20% per unit increase in terrain amplitude. Key findings include evidence that net single support work remains near zero when push-off optimally covers collision and gravity work, confirming the passive nature of single support work under this condition. We also observed that the preferred speeds for older adults tend to be 12-15% lower than for younger adults, likely due to biomechanical adaptations. Beyond certain terrain amplitudes, no preferred walking speed allowed fully passive single support work, highlighting a possible biomechanical threshold where ankle push-off alone becomes insufficient and hip torque compensation may be necessary. This approach provides a framework for estimating preferred walking speeds across different terrain amplitudes (continuous parameter), varying conditions and demographics, with potential applications in designing assistive devices and gait rehabilitation protocols that reduce metabolic cost through optimal mechanical work management.
The Powered Simplest Walking Model Explains the Different Vertical Ground Reaction Force Amplitudes at Elevated Walking Speeds
Authors: Hosseini-Yazdi Seyed-Saleh
Published: August 2024

The vertical component of walking ground reaction force (GRF) has attracted much attention in analyzing human gait. Its typical trajectory shows two peaks at the beginning and end of the stance phase. The first peak signifies step load acceptance, while the second peak is to accelerate the center of mass (COM) for the next step. As walking speed increases, these peaks grow at different rates, with the first peak’s amplitude becoming larger. No mechanistic explanation has been provided for this change. Here, we used a simple walking model and the COM work rate trajectory to investigate the vertical GRF profile change. A step is usually energized by positive work (push-off) at its start, followed by energy dissipation. It is suggested that push-off is exerted by the ankle joint. At elevated walking speeds, the ankle’s biomechanical power generation capacity may not be sufficient to energize the entire gait. Since push-off also limits the magnitude of step energy dissipation (collision), any shortfall in push-off is followed by increased collision, reflected in the first peak’s rise in vertical GRF. This is supported by the observation that collision work exceeds push-off beyond a certain walking speed threshold (even walking v = 1.35 m · s-1). Therefore, we also expect to observe different vertical GRF peak amplitudes when terrain challenges limit or disrupt the ankle’s mechanical energy output. The vertical GRF unequal peaks may indicate that lower limbs are subjected to higher dissipations that might overstress them, and the required compensation is provided by over actuating of the other joint that might yield to their faster deterioration.
The Significance of Uneven Walking Transitory Modulations in Walking Momentum Regulation and Active Work
Authors: Hosseini Yazdi Seyed Saleh
Published: August 2024

Uneven walking presents challenges such as balance maintenance and increased energetics. Beyond average step parameter variations, humans may employ transient strategies to conserve mechanical work or enhance momentum with minimal metabolic costs. Thus, we quantified mid-flight positive mechanical work induction, step length, and effective leg length modulation from four steps before to four steps after a specific encounter for young and older adults with normal and restricted lookaheads. Simulations were also conducted to assess the impact of step length or effective leg length changes on step-to-step transition or post-transition speed. We observed that young adults’ mid-flight energy inducements were focused around the encounter, influenced by lookahead state affecting modulation based on feedback or feedforward control. While with the restricted lookahead, older adults showed similar regulation, their anticipatory modulation was poorer and extended over the evaluation interval. With normal lookahead, young adults reduced step length just before the encounter, potentially increasing momentum with less heel-strike energy dissipation. Step length changes around and after the perturbation may have been passive. Older adults exhibited longer modulation periods than young adults. We also noted active leg length modulation, likely influenced by tactile sensory information. For up-steps, effective leg lengths were shorter, while for down-steps, they were longer, potentially compensatory actions to minimize COM vertical fluctuations and associated work against gravity. The amplitude of leg length modulation may have been constrained by the flexed legs walking energetic cost or and ankle range of motion. With restricted lookahead, older adults showed larger leg length modulation amplitudes.
Machine learning-based proteogenomic data modeling identifies circulating plasma biomarkers for early detection of lung cancer
Authors: Johnson Marcela A. , Hou Liping , Huang Bevan Emma , Saadatpour Assieh , Torshizi Abolfazl Doostparast
Published: August 2024

Identifying genetic variants associated with lung cancer (LC) risk and their impact on plasma protein levels is crucial for understanding LC predisposition. The discovery of risk biomarkers can enhance early LC screening protocols and improve prognostic interventions. In this study, we performed a genome-wide association analysis using the UK Biobank and FinnGen. We identified genetic variants associated with LC and protein levels leveraging the UK Biobank Pharma Proteomics Project. The dysregulated proteins were then analyzed in pre-symptomatic LC cases compared to healthy controls followed by training machine learning models to predict future LC diagnosis. We achieved median AUCs ranging from 0.79 to 0.88 (0-4 years before diagnosis/YBD), 0.73 to 0.83 (5-9YBD), and 0.78 to 0.84 (0-9YBD) based on 5-fold cross-validation. Conducting survival analysis using the 5-9YBD cohort, we identified eight proteins, including CALCB, PLAUR/uPAR, and CD74 whose higher levels were associated with worse overall survival. We also identified potential plasma biomarkers, including previously reported candidates such as CEACAM5, CXCL17, GDF15, and WFDC2, which have shown associations with future LC diagnosis. These proteins are enriched in various pathways, including cytokine signaling, interleukin regulation, neutrophil degranulation, and lung fibrosis. In conclusion, this study generates novel insights into our understanding of the genome-proteome dynamics in LC. Furthermore, our findings present a promising panel of non-invasive plasma biomarkers that hold potential to support early LC screening initiatives and enhance future diagnostic interventions.
Which Components of the Haemodynamic Response to Active Stand Predict Cardiovascular Disease and Mortality? Data From The Irish Longitudinal Study on Ageing
Authors: Hernández Belinda , Dyer Adam H. , McCrory Cathal , Newman Louise , Finucane Ciaran , Kenny Rose Anne
Published: August 2024

Background

An integrated haemodynamic response during standing may serve as an integrative marker of neuro-cardiovascular function. Individual components of both heart rate (HR) and blood pressure (BP) responses to active stand (AS) have been linked with cardiovascular disease (CVD) and mortality. We assessed longitudinal associations between entire HR/BP response curves during AS, incident CVD and mortality over 12 years.

Methods

Beat-to-beat measurements of dynamic HR/BP responses to AS were conducted in 4,336 individuals (61.5±8.2 years; 53.7% female). Functional Principal Components Analysis was applied to HR/BP response curves and their association with CVD and mortality assessed. We hypothesised that integrating BP/HR information from the entire haemodynamic response curve may uncover novel associations with both CVD and mortality.

Results

Higher systolic BP (SBP) before AS and blunted recovery of SBP during AS was associated with all-cause mortality over 12-years (Hazard Ratio [HR]: 1.14; 1.04, 1.26; p=0.007). Higher baseline/peak HR and lower HR from 30 seconds post stand onwards were associated with lower mortality due to circulatory causes (HR: 0.78; 0.64, 0.95; p = 0.013). Higher HR throughout AS was associated with mortality from other causes (HR: 1.48; 1.22, 1.80; p<0.001). Findings persisted on robust covariate adjustment.

Conclusions

We observed distinct relationships between HR/BP responses to AS and 12-year incident CVD and mortality. Integrating the entire haemodynamic response may reveal more nuanced relationships between HR/BP responses to AS, CVD and mortality - serving as an integrative marker of neuro-cardiovascular health in midlife and beyond.
A phase Ib/IIa randomized trial of Enoxacin in patients with ALS
Authors: Magen Iddo , Kaneb Hannah Marlene , Masnata Maria , Pulimood Nisha , Emde Anna , Genge Angela , Hornstein Eran
Published: August 2024

Background and Objectives

The RNAse III DICER is essential for miRNA biogenesis. DICER activity is downregulated in sporadic and genetic forms of ALS. Accordingly, hundreds of miRNAs are broadly downregulated, and their mRNA targets are de-repressed. Enoxacin is a fluoroquinolone, which increases DICER activity and miRNA biogenesis. In an investigator-initiated, first-in-patient phase Ib/IIa study, we tested Enoxacin safety and tolerability in patients with ALS and explored pharmacodynamic biomarkers for Enoxacin target engagement.

Trial design

REALS1 was a randomized, double-blind, parallel group study.

Methods

Patients with sporadic ALS who met inclusion criteria were dosed with 200mg, 400mg or 600mg oral Enoxacin twice daily for 30 days. Randomization was conducted as per a randomization sequence generated by the study statistician. The study participants, care givers, and those assessing outcomes were blinded to dose assignment throughout the study. The main objective of this trial was safety and tolerability, and primary outcomes were the number and severity of adverse events and number of patients completing dosing. Other objective was pharmacodynamic biomarkers for Enoxacin target engagement, measured by profiling miRNAs by RNA-seq.

Results

A total of eight patients were randomized to either 200mg x 2/day (n=3), 400mg x 2/day (n=3) or 600mg x 2/day (n=2). Patients did not experience any serious adverse events. One patient in the 600 mg x 2/day group discontinued the study early, due to adverse events that were not life-threatening. Molecular analysis of cell-free miRNA in plasma and CSF was performed in the 200mg x 2/day and 400mg x 2/day groups, in which all patients completed dosing. This analysis revealed a global increase in plasma and CSF miRNA levels in all post-treatment time points, compared to baseline.

Conclusion

Enoxacin is safe and tolerable and provides important evidence for in-patient target engagement. These results encourage testing Enoxacin efficacy in larger trials.

Trial Registration information

ClinicalTrials.govidentifier:NCT04840823. Submitted on March 29, 2021. First patient enrolled on April 8, 2021.

Funding

ALS Association, ALS Canada, eRARE FP7, Israel Ministry of Health, Muscular Dystrophy Canada, Canadian Institutes of Health Research and Fonds de recherche du Québec - Santé.
The oxytocin system in patients with craniopharyngioma: A systematic review
Authors: Mann Amy , Kalitsi Jennifer , Jani Khushali , Martins Daniel , Kapoor Ritika R , Paloyelis Yannis
Published: August 2024

Craniopharyngioma is a benign tumour affecting the hypothalamic and pituitary regions, which are involved in the production and secretion of oxytocin. We conducted a systematic review to assess dysregulation of the oxytocin system in craniopharyngioma and associations with neurobehavioural, eating, and metabolic abnormalities. Eight studies (n=72 patients) were included. Evidence for dysfunction of the endogenous oxytocin system in craniopharyngioma is limited and mixed. While no significant differences in baseline salivary oxytocin concentrations were reported between patients with craniopharyngioma and controls, patients with craniopharyngioma were found to have blunted salivary oxytocin response following exercise stimulation and this was associated with greater state anxiety and higher BMI. Studies administering exogenous oxytocin are sparse and do not meet required standards. Hypothalamic damage may pose an additional mechanism of oxytocin dysregulation. Improving understanding of the oxytocin system in craniopharyngioma could be pivotal for exploring the potential therapeutic role of exogenous oxytocin in this condition.
Indications and Outcome of Intravitreal Bevacizumab Injection in a Community Eye Hospital, Nepal
Authors: Thakali Sunil , Shrestha Mohini , Gauchan Aleena , Gurung Hom Bahadur , Poudel Manish
Published: August 2024

Intravitreal bevacizumab(IVB) injection, is a humanized monoclonal antibody that has been in use for the treatment of retinal diseases, very cheaply, especially for developing countries like Nepal. This is a retrospective study designed to evaluate the indications and outcomes of IVB at Hetauda Community Eye Hospital from 2019 to 2022. In this study, among 247 patients including 260 eyes with a follow-up rate of 221 patients involving 234 eyes, the mean patient age was 64.4 years, with male predominance of 56.1%. Thus, IVB was used principally in the treatment of diabetic retinopathy, neovascular age-related macular degeneration, and branch retinal vein occlusion. The results indicated significant improvements in central macular thickness and visual acuity with respect to diabetic retinopathy, nAMD, and BRVO. The study thus puts forth the effectiveness of IVB in improving visual outcomes and reducing CMT in a resource-constrained setting; hence, its use should be implemented as a viable treatment option within such an environment.
Imputing abundance of over 2500 surface proteins from single-cell transcriptomes with context-agnostic zero-shot deep ensembles
Authors: Chen Ruoqiao , Zhou Jiayu , Chen Bin
Published: August 2024

Cell surface proteins serve as primary drug targets and cell identity markers. The emergence of techniques like CITE-seq has enabled simultaneous quantification of surface protein abundance and transcript expression for multimodal data analysis within individual cells. The published data have been utilized to train machine learning models for predicting surface protein abundance based solely from transcript expression. However, the small scale of proteins predicted and the poor generalization ability for these computational approaches across diverse contexts, such as different tissues or disease states, impede their widespread adoption. Here we propose SPIDER (surface protein prediction using deep ensembles from single-cell RNA-seq), a context-agnostic zero-shot deep ensemble model, which enables the large-scale prediction of cell surface protein abundance and generalizes better to various contexts. Comprehensive benchmarking shows that SPIDER outperforms other state-of-the-art methods. Using the predicted surface abundance of >2500 proteins from single-cell transcriptomes, we demonstrate the broad applications of SPIDER including cell type annotation, biomarker/target identification, and cell-cell interaction analysis in hepatocellular carcinoma and colorectal cancer.
Metabolic modelling reveals increased autonomy and antagonism in type 2 diabetic gut microbiota
Authors: Kadibalban A. Samer , Künstner Axel , Schröder Torsten , Zauleck Julius , Witt Oliver , Marinos Georgios , Kaleta Christoph
Published: August 2024

1.

Type 2 diabetes presents a growing global health concern, with emerging evidence highlighting the pivotal role of the human gut microbiome in metabolic diseases. This study employs metabolic modelling to elucidate changes in host-microbiome interactions in type 2 diabetes. Glucose levels, dietary intake, 16S sequences and metadata were estimated and collected for a cohort of 1,866 individuals. In addition, microbial community models, as well as ecological interactions were simulated for the gut microbiomes of the cohort participants. Our findings revealed a significant decrease in the fluxes of metabolites provided by the host to the microbiome through the diet in patients with type 2 diabetes, accompanied by an increase in within-community exchanges. Moreover, the diabetic microbial community shifts towards increased exploitative ecological interactions among its member species at the expense of collaborative interactions. The reduced butyrate flux from the community to the host and reduced tryptophan acquired by the microbiome from the host’s diet further highlight the dysregulation in microbial-host interactions in diabetes. Additionally, microbiomes of type 2 diabetes patients exhibit enrichment in energy metabolism pathways, indicative of increased metabolic activity and antagonism. This study provides insights into the metabolic dynamics of the diabetic gut microbiome, shedding light on its increased autonomy and altered ecological interactions accompanying diabetes, and provides candidate metabolic targets for intervention studies and experimental validations, such as butyrate, tryptophan, H2S, several nucleotides, amino acids, and B vitamins.
Extensive mutual influences of SMC complexes shape 3D genome folding
Authors: Zhao Han , Shu Lirong , Liu Fuhai , Lin En , Xia Sijian , Wang Baiyue , Wang Manzhu , Shan Fengnian , Lin Yinzhi , Zhang Lin , Gu Yufei , Blobel Gerd A. , Zhang Haoyue
Published: August 2024

Mammalian genomes are folded by the distinct actions of SMC complexes which include the chromatin loop-extruding cohesin, the sister-chromatid cohesive cohesin, and the mitotic chromosome-associated condensins. While these complexes function at different stages of the cell cycle, they co-exist on chromatin during the G2/M-phase transition, when genome structure undergoes a dramatic reorganization. Yet, how distinct SMC complexes affect each other and how their mutual interplay orchestrates the dynamic folding of 3D genome remains elusive. Here, we engineered all possible cohesin/condensin configurations on mitotic chromosomes to delineate the concerted, mutual influential action of SMC complexes. We find that: (i) The mitotic SMC complex condensin disrupts the focal accumulation of extrusive-cohesin at CTCF binding sites, thereby promoting the disassembly of interphase TADs and chromatin loops during mitotic progression. Conversely, extrusive-cohesin can impair condensin activity and alter mitotic chromosome helicity. (ii) Condensin diminishes cohesive-cohesin focal enrichment and, conversely, cohesive-cohesin can counteract condensin function and impede mitotic chromosome longitudinal shortening. (iii) The co-presence of extrusive- and cohesive-cohesin synergistically antagonizes condensin function and dramatically delays mitotic chromosome condensation. (iv) Extrusive-cohesin positions cohesive-cohesin at CTCF binding sites. However, cohesive-cohesin by itself is insufficient to mediate the formation of TADs or chromatin loop, implying non-overlapping function with extrusive-cohesin. Instead, cohesive-cohesin restricts chromatin loop expansion, potentially by limiting extrusive-cohesin movement. Collectively, our data describe a comprehensive three-way interplay among major SMC complexes that dynamically sculpts chromatin architecture during cell cycle progression.
DNA stimulates SIRT6 to mono-ADP-ribosylate proteins within histidine repeats
Authors: Pederson Nicholas J. , Diehl Katharine L.
Published: August 2024

Sirtuins are the NAD+-dependent class III lysine deacylases (KDACs). Members of this family have been linked to longevity and a wide array of different diseases, motivating the pursuit of sirtuin modulator compounds. Sirtuin 6 (SIRT6) is a primarily nuclear KDAC that deacetylates histones to facilitate gene repression. In addition to this canonical post-translational modification (PTM) “eraser” function, SIRT6 can use NAD+instead to “write” mono-ADP-ribosylation (mARylation) on target proteins. This enzymatic function has been primarily associated with SIRT6’s role in the DNA damage response. This modification has been challenging to study because it is not clear under what precise cellular contexts it occurs, only a few substrates are known, and potential interference from other ADP-ribosyltransferases in cells, among other reasons. In this work, we used commercially available ADP-ribosylation detection reagents to investigate the mARylation activity of SIRT6 in a reconstituted system. We observed that SIRT6 is activated in its mARylation activity by binding to dsDNA ends. We further identified a surprising target motif within biochemical substrates of SIRT6, polyhistidine (polyHis) repeat tracts, that are present in several previously identified SIRT6 mARylation substrates and binding partners. This work provides important context for SIRT6 mARylation activity, in contrast to its KDAC activity, and proposes that SIRT6 is a histidine mARyltransferase enzyme.
Voronoi spatial pattern construction through bacterial colony simulation
Authors: Moreno Daniela Valentina , Ortiz Yerko Miguel , Araya Diego Ignacio , Gutierrez Martin Eduardo
Published: August 2024

Voronoi diagrams are structures that have many applications. Parallel formation of Voronoi diagrams in cell colonies is a process that would enable to study a larger array of computational and biological problems using synthetic biology on cell colonies. In this study, we propose a spatial-resolution-based solution that demonstrates the power of combining computational biology with spatial awareness. By exploring metaheuristics and defining nodes within the colony, we showcase a feasible way to address these complex problems. Our approach emphasizes the potential for Voronoi diagram construction bearing spatial considerations in bio-inspired computing, offering a novel perspective for developmental biology and potentially leading to more efficient solutions in the future. The generation of a hexagon-based pattern reminiscent of a beehive exemplifies the nature-inspired outcomes of our methodology. To achieve this, we utilize a node definition bounded by the Moore neighborhood and then assign different roles to each bacterium through cell-cell communication, allowing them to greedily color the nodes without repetition among its neighbors. To test the designed system, we utilized simulation software. The results obtained from this simulation indicate that the system approaching the Voronoi pattern relies on CRISPR for maintaining color persistence in a specific zone, irrespective of the presence of the initiating stimulus. This integration highlights its essential role in enhancing the efficiency and stability of the spatial-resolution-based approach.
Web-CONEXS: an inroad to theoretical X-ray absorption spectroscopy
Authors: Elliott Joshua D. , Rogalev Victor , Wilson Nigel , Duta Mihai , Reynolds Christopher J. , Filik Jacob , Penfold Thomas J. , Diaz-Moreno Sofia
Published: August 2024

Accurate analysis of the rich information contained within X-ray spectra usually calls for detailed electronic structure theory simulations. However, density functional theory (DFT), time-dependent DFT and many-body perturbation theory calculations increasingly require the use of advanced codes running on high-performance computing (HPC) facilities. Consequently, many researchers who would like to augment their experimental work with such simulations are hampered by the compounding of nontrivial knowledge requirements, specialist training and significant time investment. To this end, we present Web-CONEXS, an intuitive graphical web application for democratizing electronic structure theory simulations. Web-CONEXS generates and submits simulation workflows for theoretical X-ray absorption and X-ray emission spectroscopy to a remote computing cluster. In the present form, Web-CONEXS interfaces with three software packages: ORCA, FDMNES and Quantum ESPRESSO, and an extensive materials database courtesy of the Materials Project API. These software packages have been selected to model diverse materials and properties. Web-CONEXS has been conceived with the novice user in mind; job submission is limited to a subset of simulation parameters. This ensures that much of the simulation complexity is lifted and preliminary theoretical results are generated faster. Web-CONEXS can be leveraged to support beam time proposals and serve as a platform for preliminary analysis of experimental data.
Synthesis and structural characterization of a new dinuclear platinum(III) complex, [Pt2Cl4(NH3)2{μ-HN=C(O)But}2], and Synthesis and structure of two novel trans-platinum complexes. Addenda and errata
Authors: IUCr Editorial Office
Published: August 2024

This article reports changes to the authorship of two papers by Vinci & Chateigner [(2022). Acta Cryst. B78, 835–841; (2023). Acta Cryst. B79, 213–219], as well as providing additional literature citations.
Be overworked: after-hours electronic communication expectations and emotional exhaustion
Authors: Du Jingwen
Published: August 2024

Purpose

This study aimed to explore two questions. The first is why employees become emotionally exhausted when faced with after-hours electronic communication. The second is how can emotional exhaustion caused by after-hours electronic communication be alleviated?

Design/methodology/approach

Our research was based on conservation of resources theory, social exchange theory, and relative deprivation theory. We surveyed 241 employees using three waves of data collection to examine the impact of after-hours electronic communication expectations on their emotional exhaustion. We also explored the mediating effects of relative deprivation and obsessive passion from a cognitive-affective perspective and the moderating effect of leader-member exchange.

Findings

The results indicate that after-hours electronic communication expectations lead to employee emotional exhaustion, which is mediated by obsessive passion and relative deprivation. The leader-member exchange negatively moderated after-hours electronic communication expectations and relative deprivation but positively moderated after-hours electronic communication expectations and obsessive passion, thereby alleviating employee emotional exhaustion.

Originality/value

In exploring the influence mechanism of after-hours electronic communication expectations on emotional exhaustion from a cognitive-affective perspective, our study went beyond the limitations of analysis from a single perspective. A comparison of the two pathways indicated that cognition (relative deprivation) is more likely to lead to emotional exhaustion, which validates the view that individuals can ultimately analyse their behaviours rationally. By exploring the moderating effect of leader-member exchange, we provide a theoretical basis for organisations to take measures to alleviate the negative emotions caused by after-hours electronic communication.
Why is digital transformation so slow? The shadow of dehumanization 2.0
Authors: Czakon Wojciech , Meyer Natanya
Published: August 2024

Purpose

In recent years we have seen major technological advancements including the launch of large language models such as ChatGPT and the popularity of the digital transformation topic among professionals and academics. Despite this, the pace of digital transformation is surprisingly slow. We aimed to identify behavioral antecedents of an organization’s sluggish digital transformation.

Design/methodology/approach

We adopted the organizational level of analysis, which differs from prior analyses of technological revolutions that looked at the phenomenon from an aggregate labor market or society level of analysis.

Findings

We identified dehumanization as a key construct useful in examining the behavioral impediments to digital transformation. We indicated that the traditionally dual understanding of dehumanization needs to incorporate the actual involvement of non-human agents in operational and decision-making processes in organizations.

Originality/value

We complemented the predominant approach of digital transformation, which focuses on technology and related business model development, with a behavioral approach. We considered digital transformation as an extreme degree of change, similar to the Industrial Revolution. We paved the way for the conceptual development of dehumanization in the digital world and for developing managerial practices useful in alleviating concerns that impede the pace of digital transformation.
Knowledge distance and business model reconfiguration: the moderating role of tie strength
Authors: Karoui Badr Eddine , Chtourou Wafi
Published: August 2024

Purpose

The purpose of this paper is to determine how knowledge distance, which encompasses cognitive and geographic distance, influences efficiency-centered and novelty-centered business model reconfiguration (BMR), and the moderating role of tie strength.

Design/methodology/approach

The authors analyze a sample of 132 Tunisian incumbent firms by multiple hierarchical regressions.

Findings

First, the effect of knowledge distance on novelty-centered BMR may differ depending on whether the firm introduces novelty within or outside its organizational boundaries. Specifically, the authors introduce two new types of novelty-centered BMR: intra-novelty and extra-novelty, which respectively take into account whether the reconfigured activities are governed within or outside the focal firm’s boundaries. Second, cognitive distance has an inverted U-shaped effect on efficiency-centered and intra-novelty-centered BMR. Third, tie strength has a moderating role, with varying effects depending on the type of BMR pursued.

Practical implications

This study provides guidance for managers on structuring alliances and collaborations when pursuing BMR. It provides recommendations on partner characteristics, as well as relationship tie strength, that are most beneficial for different types of BMR.

Originality/value

This paper answers the call for research on how knowledge obtained from distant sources can contribute to BMR. Additionally, the paper introduces a previously absent distinction in the BMR literature. The findings suggest that studying the antecedents of BMR should not be limited to the level of design themes but also encompass the level of design elements such as governance.