Cutaneous myiasis by Calliphoridae dipterans in dogs from Chad.

Cutaneous myiasis caused by various Calliphoridae dipteran species is prevalent worldwide and is of particular veterinary and public health concern. Recently, in a scientific exploration of the Guinea Worm Eradication Program to Chad, Africa, we observed that dogs with mutilated ears, based on local awareness, were caused by cutaneous myiasis. In this study, we analyzed epidemiological, morphological, and molecular data on cutaneous myiasis in dogs from Chad. From September to October 2022, dogs (n = 1,562) from 56 villages situated along the Chari River were physically inspected for cutaneous myiasis. All larvae were collected and identified morphologically and by molecular analysis of the partial cytochrome oxidase c subunit I (COI) mitochondrial gene. The prevalence of myiasis infestation along with 95% confidence intervals (95% CI) was determined using the modified Wilson method. Myiasis was detected in dogs from 21 villages (37.5%; 95% CI 26 - 50%), predominating in the southernmost region. Of 1,562 dogs, 66 (4.22%; 95% CI 3.34 - 5.34%) were infested by calliphorid larvae, with a mean infestation of 2.28 larvae per animal (range = 1 to 24). Specimens were morphologically identified as Cordylobia anthropophaga (n = 94), Chrysomya bezziana (n = 54), and Chrysomya sp. (n = 3), which were detected in 57, eight and one dog, respectively. No co-infestations were observed. The molecular analyses confirmed the morphological identification and revealed the presence of 17 haplotypes for C. anthropophaga, 2 for C. bezziana, and one for Chrysomya sp. Our study emphasizes the veterinary importance of myiasis in dogs in Africa and proposes measures to assure their health and well-being.

Exploratory analysis of immunomodulatory factors identifies L1CAM as a prognostic marker in alveolar soft-part sarcoma.

Background: Alveolar soft-part sarcoma (ASPS) is a rare tumor driven by the ASPSCR1-TFE3 fusion protein, with a propensity for metastasis. Prognostic factors remain poorly understood, and traditional chemotherapies are largely ineffective. Recent interest lies in immune checkpoint inhibitors (ICIs), yet predictive biomarkers for treatment response are lacking. Previous studies have shown promising results with ICIs in ASPS, indicating a need for further investigation into biomarkers associated with immune response. Objectives: To identify prognostic biomarkers in ASPS and to explore the role of immune-related markers, particularly L1CAM, in predicting patient outcomes. Design: A retrospective cohort study of 19 ASPS patients registered in the GEIS database. The study involved the collection of clinical and histopathological data, followed by an analysis of immune markers and gene expression profiles to identify potential prognostic indicators. Methods: Clinical and histopathological data were retrospectively collected from the GEIS-26 study cohort of 19 ASPS patients. Immunohistochemistry was performed to evaluate immune markers programmed death-1 ligand (PD-L1), programmed death-1, FAS, FASL, CD8, CD3, and CD4. An HTG ImmunOncology panel was conducted on formalin-fixed paraffin-embedded samples to explore gene expression. Effects of differentially expressed genes on survival were explored by Kaplan-Meier. Results: PD-L1 positivity was widely observed (63%) in tumors, and CD8+ lymphocytic infiltration was common. High CD8 density correlated with greater overall survival (OS) while not statistically significant. No associations were found for other immune markers. L1CAM was identified as differentially expressed in patients with low CD8 infiltration and correlated negatively with OS. Conclusion: High L1CAM expression correlated with poorer OS, highlighting its potential as a prognostic marker and therapeutic target in ASPS. Immunomodulatory interventions may hold promise, as evidenced by PD-L1 expression and CD8+ infiltration. Further research, including larger cohorts and international collaborations, is needed to validate these findings and explore therapeutic strategies targeting L1CAM in ASPS.

Understanding immune response in a rare cancer: exploring avenues for alveolar soft-part sarcoma Why was the study done? Alveolar soft-part sarcoma (ASPS) is a rare cancer with limited treatment options. Our study aimed to understand how the immune system responds to ASPS and explore potential treatments, as current therapies are often ineffective. What did the researchers do? We analyzed data from 19 ASPS patients to investigate immune response and potential treatment targets. We examined the expression of immune markers and genes related to immune response to identify factors influencing patient outcomes. What did the researchers find? We found that most tumors showed signs of an active immune response, with a protein called PD-L1 being present. We also noticed that many tumors had a type of immune cell called CD8+ lymphocytes. Although having more of these CD8+ cells seemed to be linked to better survival, this connection wasn't strong enough to be certain. We didn't find any clear links with other immune markers we looked at. However, we did find that a protein called L1CAM was more common in patients who had fewer CD8+ cells in their tumors, and this was linked to poorer overall survival. What do the findings mean? Our study sheds light on the immune response in ASPS and identifies potential targets for therapy. By understanding these mechanisms, we hope to pave the way for more effective treatments and improve outcomes for ASPS patients in the future.

Immunologic and Targeted Molecular Therapies for Chordomas: A Narrative Review.

Chordomas are rare sarcomas arising from notochordal tissue and occur most commonly in the spine. The standard of care for chordomas without evidence of metastatic disease generally consists of en bloc resection followed by adjuvant radiotherapy. However, long-term (20-year) survival rates are approximately 30%. Chordomas are generally considered as chemo resistant. Therefore, systemic therapies have rarely been employed. Novel immunotherapies, including antibody therapy and tumor vaccines, have shown promise in early trials, leading to extended progression-free survival and symptom relief. However, the outcomes of larger trials using these vectors are heterogeneous. The aim of this review is to summarize novel chordoma treatments in immune-targeted therapies. The current merits, trial outcomes, and toxicities of these novel immune and targeted therapies, including those targeting vascular endothelial growth factor receptor (VEGFR) targets and the epidermal growth factor receptor (EGFR), will be discussed.

Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS).

PURPOSE: Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination. PATIENTS AND METHODS: Patients with advanced leiomyosarcoma and anthracycline-naïve were eligible. The initial dose level consisted of doxorubicin 75 mg/m2 once on day 1, once every three weeks, followed by dacarbazine 400 mg/m2 once on days 1 and 2, once every three weeks, plus nivolumab 360 mg once on day 2, once every 3 weeks, for six courses and then 1 year of nivolumab. A (-1) dose level was the same regimen but with nivolumab 240 mg. A classic 3 + 3 phase-I design was used to determine the recommended phase-II dose (RP2D). Secondary end points included overall response rate, safety profile, survival, and translational research. RESULTS: From January 2002 to July 2023, 24 patients were enrolled and 23 were evaluable for efficacy, excluding one patient because of noncompliant dose. All patients were treated with the initial dose level, then the RP2D. Toxicity was mild, with the most frequent being grade 4 toxicity neutropenia (16.7%) and thrombocytopenia (8.3%), while no grade 5 toxicity occurred. The centrally reviewed objective response rate was as follows: partial response 56.5%, stable disease 39.1%, and progression 4.4%. The 6-month progression-free survival (PFS) rate was 80% (95% CI, 63 to 98). Dynamic increases of HMGB1 in blood significantly correlated with longer PFS. CONCLUSION: This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.

Development of the scoliosis research society spinal deformity surgery safety checklist.

PURPOSE: Spine deformity surgery is a complex multi-step procedure that has a relatively high complication rate. The use of surgical safety checklists has been shown to reduce perioperative adverse events, but existing lists are varied and non-specific for spinal deformity surgery. Thus, the purpose of this study was to develop a comprehensive surgical checklist for complex spinal corrective surgery. METHODS: An electronic survey consisting of 187 surgical checklist items that had been developed and used by a group of SRS members over a 5-year period was distributed to the Scoliosis Research Society Safety and Value Committee membership. The survey sections included: (1) pre-operative area, (2) initial operating room visit, (3) before turning, (4) positioning, (5) prepare and drape, (6) pre-incision timeout, (7) intraoperative, (8) finishing implant placement and confirming imaging, (9) final rods and locking, (10) prior to closure, (11) closure, (12) turn to supine, and (13) checkout/debriefing. Respondents graded each item on a five-point Likert scale based on their perceived importance and feasibility for inclusion in the checklist. Features graded as "moderately important" or "very important" to include by at least 70% of respondents were considered to meet the cutoff for inclusion-based standard Delphi practices. Study data were collated using REDCap. RESULTS: A total of 25 surgeons completed the survey in its entirety. The overall checklist "package" was shortened to 9 individual checklist modules, with 2 to 16 items per checklist. In terms of individual checklist items, 40% of items (74 of 187) met the cutoff for inclusion; 17 of these items were graded as "very important," which included verifying the presence of implantable devices, reviewing the surgical plan and positioning with the surgical staff, securing the endotracheal tube, bite block confirmation, prone and lateral positioning, neuromonitoring baseline readings, double-checking that the implant screw caps were locked prior to closure, and confirming that the patient was moving bilateral lower extremities before leaving the operating room when possible. CONCLUSION: This study has led to the development of a specific spinal deformity surgical checklist of 74 (many specific to spine surgery) items that were considered important for inclusion; 17 were considered "very important".

Subclassification of obesity for precision prediction of cardiometabolic diseases.

Obesity and cardiometabolic disease often, but not always, coincide. Distinguishing subpopulations within which cardiometabolic risk diverges from the risk expected for a given body mass index (BMI) may facilitate precision prevention of cardiometabolic diseases. Accordingly, we performed unsupervised clustering in four European population-based cohorts (N ≈ 173,000). We detected five discordant profiles consisting of individuals with cardiometabolic biomarkers higher or lower than expected given their BMI, which generally increases disease risk, in total representing ~20% of the total population. Persons with discordant profiles differed from concordant individuals in prevalence and future risk of major adverse cardiovascular events (MACE) and type 2 diabetes. Subtle BMI-discordances in biomarkers affected disease risk. For instance, a 10% higher probability of having a discordant lipid profile was associated with a 5% higher risk of MACE (hazard ratio in women 1.05, 95% confidence interval 1.03, 1.06, P = 4.19 × 10-10; hazard ratio in men 1.05, 95% confidence interval 1.04, 1.06, P = 9.33 × 10-14). Multivariate prediction models for MACE and type 2 diabetes performed better when incorporating discordant profile information (likelihood ratio test P < 0.001). This enhancement represents an additional net benefit of 4-15 additional correct interventions and 37-135 additional unnecessary interventions correctly avoided for every 10,000 individuals tested.

The pace of life for forest trees.

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found emergent patterns in the strength of trade-offs between growth and longevity across a temperature gradient. Furthermore, we show that the diversity of life history traits varies predictably across forest biomes, giving rise to a positive relationship between trait diversity and productivity. Our pan-latitudinal assessment provides new insights into the demographic mechanisms that govern the carbon turnover rate across forest biomes.

Gene expression in the hypothalamic-pituitary-thyroid axis in Seriola rivoliana early larvae development at different temperatures.

We analyzed the expression of genes involved in the hypothalamic-pituitary-thyroid axis (HPT-axis) in the longfin yellowtail Seriola rivoliana early larva, including temperature effects (22, 26 and 28 °C) and days of development (day one, day two, and day six after hatching). We aimed to determine if egg and larval incubation at different temperatures could disrupt this critical endocrine axis, which, in an aquaculture context, it could provoke mortality during early metamorphosis. There was a significant interaction between temperature and developmental timing on the relative expression of thyrotropin releasing hormone (trh). Larvae at 22 °C was the longest and increased more trh expression than larvae at higher temperatures. Interestingly, thyrotropin stimulating hormone (tsh) was highly expressed after hatching. Subsequently, it was downregulated at any temperature at least until day four, suggesting a temporal inhibition of the HPT axis. Therefore, we suggest that tsh-binding (tshr) to follicles should have occurred from hatching, creating a further "cascade effect" of upregulation of larval thyroglobulin (tg) from day two in a temperature-dependent manner. Consequently, new thyroid hormones should have been produced after yolk sac absorption. The above may indicate a narrow window of larval survival, where the larval transition from endogenous to exogenous feeding would depend on the correct timing to synthesize tg. Temperature significantly affected the expressions of deiodinase 1 (dio1-downregulated) and deiodinase 2 (dio2-upregulated) after hatching. The expressions of thyroid receptors alpha (trα) and beta (trß) remained constant after hatching without significant effects of temperature and days of development. Then, the differential expression on day six showed that all HPT-axis transcripts increased their expressions as larvae developed, which suggested a functional HPT. Finally, there was no evidence that any temperature would disrupt the endocrine's larval axis, which indicated that the longfin yellowtail has a wide temperature adaption. Nevertheless, based on tg upregulation, we suggest that larvae should be maintained around 25-26 °C after hatching for a better chance of survival and development.

Therapeutic Opportunities for Biomarkers in Metastatic Spine Tumors.

For many spine surgeons, patients with metastatic cancer are often present in an emergent situation with rapidly progressive neurological dysfunction. Since the Patchell trial, scoring systems such as NOMS and SINS have emerged to guide the extent of surgical excision and fusion in the context of chemotherapy and radiation therapy. Yet, while multidisciplinary decision-making is the gold standard of cancer care, in the middle of the night, when a patient needs spinal surgery, the wealth of chemotherapy data, clinical trials, and other medical advances can feel overwhelming. The goal of this review is to provide an overview of the relevant molecular biomarkers and therapies driving patient survival in lung, breast, prostate, and renal cell cancer. We highlight the molecular differences between primary tumors (i.e., the patient's original lung cancer) and the subsequent spinal metastasis. This distinction is crucial, as there are limited data investigating how metastases respond to their primary tumor's targeted molecular therapies. Integrating information from primary and metastatic markers allows for a more comprehensive and personalized approach to cancer treatment.

Racial Disparities in Patients with Metastatic Tumors of the Spine: A Systematic Review.

OBJECTIVE: Disparities in access and delivery of care have been shown to disproportionately affect certain racial groups. Studies have been conducted to assess these disparities within the spinal metastasis population, but the extent of their effects in the setting of other socioeconomic measures remains unclear. The purpose of this study was to perform a systematic review to understand the effect of racial disparities on outcomes in patients with metastatic spine disease. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, where a comprehensive online search was performed using Pubmed, Medline, Web of Science, Cochrane, Embase, and Science Direct using MeSH terms related to metastatic spine tumor surgery and racial disparities up to February 2023. Two independent reviewers screened and analyzed articles to include studies assessing the following primary outcomes: clinical presentation, treatment type, postoperative complications, readmission, reoperation, survival and/or mortality, length of hospital stay, discharge disposition, and advance care planning. RESULTS: A total of 13 studies were included in final analysis; 12 were retrospective cohort studies (Level of evidence III) and 1 was a prospective study (Level of evidence II). Postoperative complications were the most studied outcome in 46% of studies (6 of 13), followed by survival in 31% (4 of 13), and treatment type also in 31% (4 of 13). Overall, race was found to be significantly associated with at least one evaluated outcome in 69% of studies (9 of 13). Racial disparities were found in the incidence of cord compression, non-routine discharge, and treatment type in patients with metastatic spine disease. No differences were found on rates of post-operative ambulation, advance care planning, readmission, or survival; inconsistent results were seen for postoperative complications and length of stay. Nine studies (69%) included at least one other measure of socioeconomic status in multivariate analysis, with the two most common being insurance type and income. CONCLUSIONS: Although some studies suggest race to be associated with presenting characteristics, treatment type and outcome of patients with spinal metastases, there was significant variability in the inclusion of measures of socioeconomic status in study analyses. As such, the association between race and outcomes in oncologic spine surgery remains unclear.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in KIT and PDGFRA genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis. METHODS: Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed. RESULTS: Both patients harbouring low-risk GISTs with different mutations (PDGFRA and KIT) shared homozygous germline pathogenic deletions in both CFHR1 and CFHR3 genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as SLC25A24. No particular pathogenic SNV shared by both patients was detected. CONCLUSION: Our study provides new insights into germline variants that can be associated with the development of GISTs, namely, CFHR1 and CFHR3 deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

Association between different diet quality scores and depression risk: the REGICOR population-based cohort study.

BACKGROUND: Our aim was to determine the association between diet quality and depression incidence in the population-based REGICOR cohort study, Catalonia, Spain. METHODS: Prospective observational study using participants' baseline (2003-2006), follow-up (2007-2013) and clinical records data. Five diet quality scores were derived from a food frequency questionnaire (FFQ) at baseline: the relative Mediterranean Diet Score (rMED), the Modified Mediterranean Diet Score (ModMDS), a Dietary Approaches to Stop Hypertension (DASH) score, a Healthful Plant-based Diet Index (HPDI) and the World Health Organization Healthy Diet Indicator (WHO-HDI). Participants using pharmacological antidepressant treatment were excluded as a proxy for presence of depression at baseline. At follow-up, the Patient Health Questionnaire (PHQ-9) was applied to assess depressive symptoms (≥ 10 defining depressive disorder). A secondary outcome was depression diagnosis assessed through clinical records. Logistic regression and Cox proportional hazards models were used. RESULTS: Main analysis included 3046 adults (50.3% women) with a mean age of 54.7 (SD = 11.6) years. After 6-years follow-up, 184 (6.04%) cases of depressive disorder were identified. There was 16% lower odds of depressive disorder per 1SD increase of rMED (OR = 0.84; 95%CI = 0.71-0.98). Secondary outcome analysis (n = 4789) identified 261 (5.45%) incident cases of clinical depression diagnosis over 12 years follow-up, and 19% lower risk of clinical depression was observed with the WHO-HDI (HR = 0.81; 95%CI = 0.70-0.93). Adjusting for BMI did not attenuate the findings. CONCLUSIONS: A significant inverse association between diet quality and depression incidence was found in this population-based cohort study, independent of sociodemographic, health and lifestyle. Adherence to a healthy diet could be a complementary intervention for the prevention of depression.

Development of a natural language processing algorithm for the detection of spinal metastasis based on magnetic resonance imaging reports.

Background: Metastasis to the spinal column is a common complication of malignancy, potentially causing pain and neurologic injury. An automated system to identify and refer patients with spinal metastases can help overcome barriers to timely treatment. We describe the training, optimization and validation of a natural language processing algorithm to identify the presence of vertebral metastasis and metastatic epidural cord compression (MECC) from radiology reports of spinal MRIs. Methods: Reports from patients with spine MRI studies performed between January 1, 2008 and April 14, 2019 were reviewed by a team of radiologists to assess for the presence of cancer and generate a labeled dataset for model training. Using regular expression, impression sections were extracted from the reports and converted to all lower-case letters with all nonalphabetic characters removed. The reports were then tokenized and vectorized using the doc2vec algorithm. These were then used to train a neural network to predict the likelihood of spinal tumor or MECC. For each report, the model provided a number from 0 to 1 corresponding to its impression. We then obtained 111 MRI reports from outside the test set, 92 manually labeled negative and 19 with MECC to test the model's performance. Results: About 37,579 radiology reports were reviewed. About 36,676 were labeled negative, and 903 with MECC. We chose a cutoff of 0.02 as a positive result to optimize for a low false negative rate. At this threshold we found a 100% sensitivity rate with a low false positive rate of 2.2%. Conclusions: The NLP model described predicts the presence of spinal tumor and MECC in spine MRI reports with high accuracy. We plan to implement the algorithm into our EMR to allow for faster referral of these patients to appropriate specialists, allowing for reduced morbidity and increased survival.

Prognostic impact of tumor location and gene expression profile in sporadic desmoid tumor.

PURPOSE: Prognostic biomarkers remain necessary in sporadic desmoid tumor (DT) because the clinical course is unpredictable. DT location along with gene expression between thoracic and abdominal wall locations was analyzed. METHOD: Sporadic DT patients (GEIS Registry) diagnosed between 1982 and 2018 who underwent upfront surgery were enrolled retrospectively in this study. The primary endpoint was relapse-free survival (RFS). Additionally, the gene expression profile was analyzed in DT localized in the thoracic or abdominal wall, harboring the most frequent CTNNB1 T41A mutation. RESULTS: From a total of 454 DT patients, 197 patients with sporadic DT were selected. The median age was 38.2 years (1.8-89.1) with a male/female distribution of 33.5/66.5. Most of them harbored the CTNNB1 T41A mutation (71.6 %), followed by S45F (17.8 %) and S45P (4.1 %). A significant worse median RFS was associated with males (p = 0.019), tumor size ≥ 6 cm (p = 0.001), extra-abdominal DT location (p < 0.001) and the presence of CTNNB1 S45F mutation (p = 0.013). In the multivariate analysis, extra-abdominal DT location, CTNNB1 S45F mutation and tumor size were independent prognostic biomarkers for worse RFS. DTs harboring the CTNNB1 T41A mutation showed overexpression of DUSP1, SOCS1, EGR1, FOS, LIF, MYC, SGK1, SLC2A3, and IER3, and underexpression of BMP4, PMS2, HOXA9, and WISP1 in thoracic versus abdominal wall locations. CONCLUSION: Sporadic DT location exhibits a different prognosis in terms of RFS favoring the abdominal wall compared to extra-abdominal sites. A differential gene expression profile under the same CTNNB1 T41A mutation is observed in the abdominal wall versus the thoracic wall, mainly affecting the Wnt/ß-catenin, TGFß, IFN, and TNF pathways.

Predictors of Clavien-Dindo Grade III-IV or Grade V Complications after Metastatic Spinal Tumor Surgery: An Analysis of Sociodemographic, Socioeconomic, Clinical, Oncologic, and Operative Parameters.

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such as sociodemographic or socioeconomic data on outcomes. We retrospectively analyzed data from 165 patients who underwent surgery for spinal metastases between 2012-2023. The primary outcome was development of major complications (i.e., Clavien-Dindo Grade III-IV complications), and the secondary outcome was 30-day mortality (i.e., Clavien-Dindo Grade V complications). An exploratory data analysis that included sociodemographic, socioeconomic, clinical, oncologic, and operative parameters was performed. Following multivariable analysis, independent predictors of Clavien-Dindo Grade III-IV complications were Frankel Grade A-C, lower modified Bauer score, and lower Prognostic Nutritional Index. Independent predictors of Clavien-Dindo Grade V complications) were lung primary cancer, lower modified Bauer score, lower Prognostic Nutritional Index, and use of internal fixation. No sociodemographic or socioeconomic factor was associated with either outcome. Sociodemographic and socioeconomic factors did not impact short-term surgical outcomes for metastatic spinal tumor patients in this study. Optimization of modifiable factors like nutritional status may be more important in improving outcomes in this complex patient population.

Nonquantitative CT scan Hounsfield unit as a determinant of cervical spine bone density.

OBJECTIVE: Hounsfield unit (HU) values measured using CT have been increasingly recognized to stand as a reliable corollary to dual-energy x-ray absorptiometry (DEXA) scores in evaluating bone mineral density. The authors examined the correlation between cervical HU values and DEXA T- and Z-scores and determined novel cervical HU thresholds for determining bone quality classification. METHODS: One hundred patients who underwent both cervical spine CT and DEXA, 85 patients who underwent both lumbar CT and DEXA, and 128 patients who underwent cervical and lumbar CT within 24 months at a single institution were included in this retrospective review. Two independent reviewers collected HU values from 3 cervical vertebral levels (C4-6) and 4 lumbar vertebral levels (L1-4), and the averaged values were used. Pearson's correlation coefficient analysis was performed to compare the association of cervical HU values with lumbar HU values and T- and Z-scores. The mean cervical HU values for each DEXA classification were calculated and compared. Receiver operating characteristic (ROC) curves were created to determine the threshold and its sensitivity and specificity for diagnosis. RESULTS: Cervical (C4-6) HU values and average, lumbar, and femoral T- and Z-scores had significant correlations (0.436 > r > 0.274, all p < 0.01). A strong positive correlation between cervical and lumbar HU values was found (r = 0.79, p < 0.01). The average cervical HU value of healthy patients was 361.2 (95% CI 337.1-385.3); of osteopenic patients, 312.1 (95% CI 290.3-333.8); and of osteoporotic patients, 288.4 (95% CI 262.6-314.3). There was a significant difference between the cervical HU values of healthy and osteopenic patients (p = 0.0134) and between those of healthy and osteoporotic patients (p = 0.0304). The cervical HU value of 340.98 was 73.5% specific and 57.9% sensitive for diagnosing osteopenia with an area under the ROC (AUROC) curve of 0.655. The cervical HU value of 326.5 was 88.9% specific and 63.2% sensitive for diagnosing osteoporosis with an AUROC curve of 0.749. CONCLUSIONS: This is the second large-scale study and first with a patient population from the United States to show that HU values obtained using cervical CT were significantly correlated with bone quality based on DEXA T- and Z-scores and to establish a cervical HU threshold for determining bone quality classification. These results show that cervical HU values can and should be used to predict poor bone quality in surgical cervical spine patients.

Dirofilaria immitis and Dirofilaria striata (Spirurida: Onchocercidae) detected in wild carnivores from Texas, United States.

Dirofilaria immitis and Dirofilaria striata (Spirurida: Onchocercidae) are epidemiologically important filarial nematodes detected in wild carnivores sympatric to domestic animals and humans. In this study we surveyed for Dirofilaria species among previous studies archived blood samples (n = 202) of wild carnivores sourced across Texas between the years of 2014-2016 and 2020 to 2023. In total, 117 coyotes (Canis latrans), 67 raccoons (Procyon lotor), 12 gray foxes (Urocyon cinereoargenteus), five bobcats (Lynx rufus), and one striped skunk (Mephitis mephitis) were tested through the amplification of the partial cytochrome oxidase c subunit 1 (COI) gene followed by sequencing. Dirofilaria immitis was detected in 11.39% (95% CI = 7.71-16.51) of the samples (21 coyotes and two raccoons), while D. striata was detected in a single bobcat. Dirofilaria immitis sequences had 99.85%-100% (99.92% ± 0.08) similarity with other D. immitis sequences in GenBank. The sequence of D. striata from the bobcat was 100% similar to the single COI sequence available in GenBank. Data from this study reinforce the role of coyotes as a wild reservoir for D. immitis and suggest that raccoons may also play a role in the epidemiology of this parasite. This study additionally provides molecular data on D. striata, an understudied filarioid of felids.

Heterocycles as supramolecular handles for crystal engineering: a case study with 7-(diethylamino)coumarin derivatives.

In this study, we present the synthesis and detailed solid-state structural characterization of a Schiff-base-bridged derivative of 7-(diethylamino)coumarin (7-DAC), a molecular block displaying repetitive aggregation modes in the solid state despite being attached to broadly different molecular frameworks. To map the supramolecular habits of this unconventional moiety, we carry out a comparative analysis of the crystal packing in a curated dataset of 50 molecules decorated with the 7-DAC group, retrieved from the literature. We uncover that self-recognition of the 7-DAC moiety has two main components: a set of directional C-H⋯O interactions between neighboring coumarins, and antiparallel dipole-dipole interactions, taking the form of distinct π-stacking modes. The pendant 7-diethylamino group is key to the behavior of 7-DAC, favoring its solubilization through its conformational flexibility in solution, while in the crystalline matrix, it acts as a structural spacer that favors π-stacking interactions. Our findings present a comprehensive analysis of the preferential arrangements of the 7-DAC fragment in various (supra)molecular scenarios, confirming that it is (i) a mobile but mostly planar group, (ii) a group prone to antiparallel aggregation, and (iii) up to 90% likely to pack via π-stacking supported by hydrogen-bonding interactions. These findings enrich the palette of supramolecular motifs available for the bottom-up design of organic materials and their programmed construction.

Metformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men.

BACKGROUND: An altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D. AIM: To investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. METHODS: We explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (n = 172); (2) people with long-term T2D on metformin monotherapy (n = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (n = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (n = 22). Analyses were also performed stratifying by sex. RESULTS: Several bacterial species belonging to the Proteobacteria (Escherichia coli) and Verrucomicrobia (Akkermansia muciniphila) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (Romboutsia timonensis, Romboutsia ilealis) were negatively associated. Due to the consistent increase in A. muciniphila and decrease in R.ilealis in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the A.muciniphila/R.ilealis ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the A.muciniphila/R. ilealis ratio was significantly and positively associated with higher memory scores and improved memory in men. Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved in arginine metabolism, especially in production of glutamate (astA, astB, astC, astD, astE, putA), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate. CONCLUSIONS: The beneficial effects of metformin may be mediated by changes in the composition of the gut microbiota and microbial-host-derived co-metabolites.

Area Socioeconomic Status is Associated with Refusal of Recommended Surgery in Patients with Metastatic Bone and Joint Disease.

BACKGROUND: This study sought to identify associations between the Yost Index, a geocoded area neighborhood socioeconomic status (nSES) score, and race/ethnicity with patient refusal of recommended surgery for metastatic bone disease. METHODS: Patients with metastatic bone disease were extracted from the Surveillance, Epidemiology, and End Results database. The Yost Index was geocoded using factor analysis and categorized into quintiles using census tract-level American Community Service (ACS) 5-year estimates and seven nSES measures. Multivariable logistic regression models calculated odds ratios (ORs) of refusal of recommended surgery and 95% confidence intervals (CIs), adjusting for clinical covariates. RESULTS: A total of 138,257 patients were included, of which 14,943 (10.8%) were recommended for surgical resection. Patients in the lowest nSES quintile had 57% higher odds of refusing surgical treatment than those in the highest quintile (aOR = 1.57, 95% CI 1.30-1.91, p < 0.001). Patients in the lowest nSES quintile also had a 31.2% higher age-adjusted incidence rate of not being recommended for surgery compared with those in the highest quintile (186.4 vs. 142.1 per 1 million, p < 0.001). Black patients had 34% higher odds of refusing treatment compared with White patients (aOR = 1.34, 95% CI 1.14-1.58, p = 0.003). Advanced age, unmarried status, and patients with aggressive cancer subtypes were associated with higher odds of refusing surgery (p < 0.001). CONCLUSIONS: nSES and race/ethnicity are independent predictors of a patient refusing surgery for metastatic cancer to bone, even after adjusting for various clinical covariates. Effective strategies for addressing these inequalities and improving the access and quality of care of patients with a lower nSES and minority backgrounds are needed.