Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy.

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also been thoroughly studied and has shown promise in selected cases. In this review, we summarize the progress in the understanding of the genetic landscape and the cellular and molecular basis of radioiodine refractory-DTC and ATC, as well as discuss the current treatment options and future therapeutic avenues.

Surgical Management of Chronic Neuropathic Burn Pain.

Burn-related chronic neuropathic pain can contribute to a decreased quality of life. When medical and pharmacologic therapies prove ineffective, patients should undergo evaluation for surgical intervention, consisting of a detailed physical examination and elective diagnostic nerve block, to identify an anatomic cause of pain. Based on symptoms and physical examination findings, particularly Tinel's sign, treatments can vary, including a trial of laser therapies, fat grafting, or nerve surgeries (nerve decompression, neuroma excision, targeted muscle reinnervation, regenerative peripheral nerve interfaces, and vascularized denervated muscle targets). It is essential to counsel patients to establish appropriate expectations prior to treatment with a multidisciplinary team.

High-Density Porous Polyethylene Implant Cranioplasty: A Systematic Review of Outcomes.

Porous polyethylene has been widely used in craniofacial reconstruction due to its biomechanical properties and ease of handling. The objective of this study was to perform a systematic review of the literature to summarize outcomes utilizing high-density porous polyethylene (HDPP) implants in cranioplasty. A literature search of PubMed, Cochrane Library, and Scopus databases was conducted to identify original studies with HDPP cranioplasty from inception to March 2023. Non-English articles, commentaries, absent indications or outcomes, and nonclinical studies were excluded. Data on patient demographics, indications, defect size and location, outcomes, and patient satisfaction were extracted. Summary statistics were calculated using weighted averages based on the available reported data. A total of 1089 patients involving 1104 cranioplasty procedures with HDPP were identified. Patients' mean age was 44.0 years (range 2 to 83 y). The mean follow-up duration was 32.0 months (range 2 wk to 8 y). Two studies comprising 17 patients (1.6%) included only pediatric patients. Alloplastic cranioplasty was required after treatment of cerebrovascular diseases (50.9%), tumor excision (32.0%), trauma (11.4%), trigeminal neuralgia/epilepsy (3.4%), and others such as abscesses/cysts (1.4%). The size of the defect ranged from 3 to 340 cm 2 . An overall postoperative complication rate of 2.3% was identified, especially in patients who had previously undergone surgery at the same site. When data were available, contour improvement and high patient satisfaction were reported in 98.8% and 98.3% of the patients. HDPP implants exhibit favorable outcomes for reconstruction of skull defects. Higher complication rates may be anticipated in secondary cranioplasty cases.

Evaluation of predictive factors of septic wrist to avoid overdiagnosis.

BACKGROUND: The existing diagnostic criteria for septic wrist are nonspecific, exposing patients with noninfectious etiologies to surgical morbidity. This study aimed to identify predictors differentiating septic wrist from other etiologies. METHODS: An institutional review board-approved retrospective review was conducted on patients with a presumed diagnosis of septic wrist (2003-2022). Bivariate and multiple regression analyses were performed to identify correlation between confirmed septic wrist and comorbidities (autoimmune diseases, immunosuppression, crystalline arthropathy, intravenous [IV] drug use, smoking), penetrating trauma, fever, multi-joint involvement, inflammatory markers (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP]/white blood cells [WBC]), serum uric acid level, blood cultures, imaging findings, and synovial fluid analysis. Categorical data were reported as median [interquartile range]. RESULTS: Hundred and sixty-eight (58 females and 110 males) patients were included. The median length of hospitalization and follow-up were 6[7] days and 1[3] months. Eighty-nine (53%) patients had septic wrist confirmed with Gram stain/culture, 48 (29%) patients received alternative diagnoses, and 31 (18%) patients had undetermined diagnoses. Concomitant septic wrist and crystalline arthropathy were identified in 9 patients (6.6% of total patients). Out of the 48 patients who received alternative diagnoses, 12 (25%) underwent open drainage. Elevated synovial WBC count (95,409.4 ± 85,926.2) showed a trend of association with septic wrist (p = 0.08). Negative synovial crystals (p = 0.01), positive blood culture (p = 0.04), negative history of crystalline arthropathy (p = 0.08), and multi-joint involvement (p = 0.05) were identified as predictors of septic wrist with a combined sensitivity of 87.5%, specificity of 86.2%, and area under the curve 0.93. CONCLUSIONS: Current diagnostic criteria for septic wrist have low specificity. Negative history of crystalline arthropathy, multi-joint involvement, absence of synovial crystals, and positive blood culture are helpful indicators for predicting septic wrist in patients presenting with a painful, erythematous, and swollen wrist.

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Outpatient paracentesis for the management of ovarian hyperstimulation syndrome: study protocol for the STOP-OHSS randomised controlled trial.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is the most significant short-term complication of pharmacological ovarian stimulation. Symptoms range from mild abdominal discomfort to rare complications such as renal failure, thromboembolism and respiratory distress syndrome.Currently, clinical practice typically involves monitoring the patient until the condition becomes severe, at which point they are admitted to hospital, where drainage of ascitic fluid (paracentesis) may take place. Preliminary studies have indicated that earlier outpatient paracentesis may reduce the progression of OHSS and prevent hospitalisation in women. METHODS AND ANALYSIS: This UK, multicentre, pragmatic, two-arm, parallel-group, adaptive (group sequential with one interim analysis), open-label, superiority, confirmatory, group sequential, individually randomised controlled trial, with internal pilot will assess the clinical and cost-effectiveness and safety of outpatient paracentesis versus conservative management (usual care) for moderate or severe OHSS. 224 women from 20 National Health Service and private fertility units will be randomised (1:1) and followed up for up to 13.5 months. The primary outcome is the rate of OHSS related hospital admission of at least 24 hours within 28 days postrandomisation. The primary analysis will be an intention to treat with difference in hospitalisation rates as measure of treatment effect. Secondary outcomes include time to resolution of symptoms, patient satisfaction, adverse events and cost-effectiveness. A qualitative substudy will facilitate the feasibility of recruitment. Participant recruitment commenced in June 2022. ETHICS AND DISSEMINATION: London-Southeast Research Ethics Committee approved the protocol (reference: 22/LO/0015). Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences, as well as being disseminated to trial participants and patient groups. TRIAL REGISTRATION NUMBER: ISRCTN71978064.

Ultrastructural cilia defects in multi-ciliated uterine glandular epithelial cells from women with reproductive failure.

In brief: The causes of subfertility and recurrent pregnancy loss are often unclear. This study shows that endometrial gland cilia from women with subfertility have ultrastructural defects. Abstract: Endometrial glands secrete products into the endometrium and are necessary for embryo implantation and successful pregnancy. However, structural and functional abnormalities in endometrial gland cilia from women with reproductive failure remain poorly understood. This was a cross-sectional study where endometrial biopsies were collected at days 19-23 of the menstrual cycle from women with unexplained recurrent pregnancy loss (n = 15), unexplained subfertility (n = 11) or from egg donor control participants (n = 10). Endometrial gland cilia ultrastructure was imaged by transmission electron microscopy and cilia defects assessed by an electron-microscopist from a national primary ciliary dyskinesia diagnostic centre. Endometrial glands were isolated, and the cilia beat frequency recorded by high speed video. Subfertile women have proportionately lower ultrastructurally normal cilia (P < 0.05); higher frequency of absent dynamin arms (P < 0.01) or inner arm defects (P < 0.01) and lower cilia beat frequency (P < 0.05). The mechanisms underlying these obversions have yet to be determined. Recent studies have identified cilia related gene expression changes associated with reproductive failure and this study adds to the growing body of literature revealing structural and functional changes. The observation that cilia defects occurred at a higher frequency in endometrial glands of subfertile women raises the question of its mechanistic role in implantation.

Development and validation of survival nomograms for patients with differentiated thyroid cancer with distant metastases: a SEER Program-based study.

BACKGROUND: We aimed to develop a nomogram model of overall survival (OS) and cancer-specific survival (CSS) in patients with differentiated thyroid cancer with distant metastases, and to evaluate and validate the nomogram. Also, its prognostic value was compared with that of the 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8SS). METHODS: Patients with distant metastatic differentiated thyroid cancer (DMDTC) from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. A total of 906 patients were divided into a training set (n = 634) and validation set (n = 272). OS and CSS were selected as the primary end point and secondary end point. LASSO regression analysis and multivariate Cox regression analysis were applied to screen variables for constructing OS and CSS nomograms for survival probability at 3, 5, and 10 years. Nomograms were evaluated and validated using the consistency index (C-index), time-dependent receiver operator characteristic (ROC) curves, area under the ROC curve, calibration curves, and decision curve analysis (DCA). The predictive survival of the nomogram was compared with that of AJCC8SS. Kaplan-Meier curves and log-rank tests were used to evaluate the risk-stratification ability OS and CSS nomograms. RESULTS: CS and CSS nomograms included six independent predictors: age, marital status, type of surgical procedure, lymphadenectomy, radiotherapy, and T stage. The C-index for the OS nomogram was 0.7474 (95% CI = 0.7199-0.775), and that for the CSS nomogram was 0.7572 (0.7281-0.7862). The nomogram showed good agreement with the "ideal" calibration curve in the training set and validation sets. DCA confirmed that the survival probability predicted by the nomogram had high clinical predictive value. The nomogram could stratify patients more accurately, and showed more robust accuracy and predictive power, than AJCC8SS. CONCLUSIONS: We established and validated prognostic nomograms for patients with DMDTC, which had significant clinical value compared with AJCC8SS.

Management of Acute Carpal Tunnel Syndrome: A Systematic Review.

Purpose: This review aims to compare recovery outcomes of conservative, early operative, and a combination of conservative and operative management for acute carpal tunnel syndrome (ACTS). Methods: A literature search of PubMed, Scopus, and CINAHL from 1970 to 2022 was conducted using the keywords carpal tunnel syndrome and acute nerve compression. ACTS was defined as a case within 12 weeks of symptom onset. Primary data extracted included causes (traumatic or atraumatic), symptom duration (<1 day, 1-7 days, or 8-84 days), intervention (surgical, conservative, or conservative then surgical), follow-up duration, and outcome (full recovery or non-full recovery). Logistic regression analyses and χ2 tests were performed to investigate associations among these variables. Results: A total of 197 patients involving 127 (64.5%) traumatic and 70 (35.3%) atraumatic cases were included. Forty-seven percent of patients were managed conservatively followed by surgery, 30% conservative only, and 23% surgery only. The traumatic group was associated with better recovery than the atraumatic group. Recovery outcomes were not associated with symptom duration or follow-up time. The choice of intervention was not associated with traumatic or atraumatic etiology, nor did it affect recovery outcomes in either group. Conclusions: Traumatic ACTS is associated with better recovery outcomes than atraumatic etiologies. Surgical intervention was not found to be associated with better outcomes than conservative management, regardless of the etiologies. Further prospective studies are warranted to compare surgical versus conservative management. Clinical Relevance: Currently, there are no guidelines for the best management of ACTS, and it is not known if early or delayed surgical treatment is optimal. This review compiles the current evidence and identifies gaps in the literature, highlighting the need for further investigation to provide the best clinical practice.

Tissue adjuncts in primary cleft palate reconstruction: A systematic review.

BACKGROUND: Tissue adjunct is non-palatal tissue used to manage tension at the defect site by providing additional coverage. This review aimed to compare outcomes of various adjuncts employed in primary palatoplasty. METHODS: A literature search was conducted of MEDLINE, EMBASE, and Cochrane Library with keywords cleft palate, palatoplasty, surgical flaps, and allografts. Data extracted included demographics, cleft severity, primary/adjunctive techniques, outcomes, and follow-up periods. Logistic regression analyses and chi-squared tests were performed to investigate associations among variables. RESULTS: A total of 1332 patients (aged 3 months-5 years) with follow-up of 1 month to 21 years were included. Cleft severity included submucous cleft (1.7%), Veau I/II (33.3%), Veau III (46.3%), and Veau IV (15.1%). Most reported techniques were Furlow (52%) and intravelar veloplasty (14.3%) for soft palate, Bardach (27.2%), and V-Y Pushback (11.1%) for hard palate. Buccal myomucosal flap (BMMF) was performed in 45.4% of cases, followed by buccal fat pad flap/graft (BFP) in 40.8% and acellular dermal matrix (ADM) in 14%. Severe clefts (Veau III/IV) were repaired more frequently with BMMF compared with ADM (p = 0.003) and BFP (p = 0.01). Oronasal fistula occurred in 3.1% of patients, and velopharyngeal insufficiency (VPI) in 4%, both associated with Veau IV (fistula: p = 0.002, VPI: p = 0.0002). No significant differences were found in fistula (p = 0.79) or VPI (p = 0.14) rates between adjuncts. In severe clefts (Veau III/IV), ADM was associated with fistula formation (p = 0.03). CONCLUSIONS: Adjuncts in primary palatoplasty may mitigate unfavorable outcomes associated with severe clefts. BMMF is superior, given its inherent tissue properties, whereas BFP is effective in reducing fistula formation.

The Potential Role of Exosomes in Aesthetic Plastic Surgery: A Review of Current Literature.

Despite an increasing surge of exosome use throughout the aesthetic arena, a paucity of published exosome-based literature exists. Exosomes are membrane-bound extracellular vesicles derived from various cell types, exerting effects via intercellular communication and regulation of several signaling pathways. The purpose of this review was to summarize published articles elucidating mechanisms and potential applications, report available products and clinical techniques, and prompt further investigation of this emerging treatment within the plastic surgery community. Methods: A literature review was performed using PubMed with keywords exosomes, secretomes, extracellular vesicles, plastic surgery, skin rejuvenation, scar revision, hair growth, body contouring, and breast augmentation. Publications from 2010 to 2021 were analyzed for relevance and level of evidence. A Google search identified exosome distributors, where manufacturing/procurement details, price, efficacy, and clinical indications for use were obtained by direct contact and summarized in table format. Results: Exosomes are currently derived from bone marrow, placental, adipose, and umbilical cord tissue. Laboratory-based exosome studies demonstrate enhanced outcomes in skin rejuvenation, scar revision, hair restoration, and fat graft survival on the macro and micro levels. Clinical studies are limited to anecdotal results. Prices vary considerably from $60 to nearly $5000 based on company, source tissue, and exosome concentration. No exosome-based products are currently Food and Drug Administration-approved. Conclusions: Administered alone or as an adjunct, current reports show promise in several areas of aesthetic plastic surgery. However, ongoing investigation is warranted to further delineate concentration, application, safety profile, and overall outcome efficacy.

Comparing the educational quality of free flap technique videos on public and paid platforms.

BACKGROUND: Surgical videos are reshaping the landscape for surgical education. As this form of education has rapidly grown and become a valuable resource for experienced surgeons, residents, and students, there is great variability in the presentation of what is offered. This study aimed to assess and compare the educational quality of free flap instructional videos on public and paid platforms. METHODS: Free flap videos from public (YouTube) and paid (American Society of Plastic Surgeons Education Network and Plastic and Reconstructive Surgery Journal) sources were screened independently by three reviewers. Sample size was calculated to reach 80% power. The educational quality of the videos was determined using a modified version of Laparoscopic Surgery Video Educational Guidelines (0-6 low, 7-12 medium, 13-18 high). Professionally-made videos were identified per lighting, positioning, and video/imaging quality. Interrater reliability between the three reviewers was calculated. The educational quality of the videos was compared between public and paid sources using Mood's median test. Pearson's correlation coefficient was utilized to assess the correlation between video length and educational quality. RESULTS: Seventy-six videos were included (40 public, 36 paid). The median video lengths for public and paid platforms were 9.43(IQR = 12.33) and 5.07(IQR = 6.4) min, respectively. There were 18 high, 16 medium, and 6 low-quality public videos, versus 13 high, 21 medium, and 2 low-quality paid videos. Four public and seven paid videos were identified as professionally made. Interrater reliability was high (α = .9). No differences in educational quality were identified between public and paid platforms. Video length was not correlated with quality (p = .15). A video library compiling public high-quality videos was created (https://www.youtube.com/playlist?list=PL-d5BBgQF75VWSkbvEq6mfYI--9579oPK). CONCLUSIONS: Public and paid platforms may provide similar surgical education on free tissue transfer. Therefore, whether to subscribe to a paid video platform for supplemental free flap education should be determined on an individual basis.

A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Zanubrutinib with Rifabutin in Healthy Volunteers.

Zanubrutinib is a second-generation Bruton tyrosine kinase inhibitor that is primarily metabolized by CYP3A enzymes. Previous drug-drug interaction (DDI) studies have demonstrated that co-administration of zanubrutinib with rifampin, a strong CYP3A inducer, reduces zanubrutinib plasma concentrations, potentially impacting activity. The impact of the co-administration of zanubrutinib with less potent CYP3A inducers is unclear. This phase 1, open-label, fixed-sequence DDI study evaluated the pharmacokinetics, safety, and tolerability of zanubrutinib when co-administered with steady-state rifabutin, a known CYP3A inducer less potent than rifampin, in 13 healthy male volunteers (NCT04470908). Co-administration of zanubrutinib with rifabutin resulted in a less than 2-fold reduction of zanubrutinib exposures. Overall, zanubrutinib was well tolerated. The results of this study provide useful information for the evaluation of the DDI between rifabutin and zanubrutinib. In conjunction with safety and efficacy data from other clinical studies, these results will be taken into consideration to determine the appropriate dose recommendation of zanubrutinib when co-administered with CYP3A inducers.

Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics.

The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.

Item response theory analysis of the Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS-16) scale in a university student sample.

Unhelpful beliefs about sleep have been shown to exacerbate distress associated with sleep-related difficulties. University students are particularly vulnerable to experiencing sleep-related problems. The Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS-16) scale is a widely used instrument that assesses for sleep-disruptive cognitions. Although psychometric support for the DBAS-16 is available, Item Response Theory (IRT) analysis is needed to examine its properties at the item level. Psychometric investigation in non-clinical samples can help identify people who may be at risk for developing sleep problems. We examined the DBAS-16 using IRT on a sample of 759 university students. Our results identified items and subscales that adequately/inadequately differentiated between students who held unhelpful beliefs about sleep and those who did not. The DBAS-16 is a valuable instrument to assess unhelpful beliefs about sleep. We outline recommendations to improve the discriminatory ability of the instrument. Future investigations should establish cross-validation with a clinical sample.

Adaptive Gaussian Markov random field spatiotemporal models for infectious disease mapping and forecasting.

Recent disease mapping literature presents adaptively parameterized spatiotemporal (ST) autoregressive (AR) or conditional autoregressive (CAR) models for Bayesian prediction of COVID-19 infection risks. These models were motivated to capture complex spatiotemporal dynamics and heterogeneities of infection risks. In the present paper, we synthesize, generalize, and unify the ST AR and CAR model constructions for models augmented by adaptive Gaussian Markov random fields, with an emphasis on disease forecasting. A general convolution construction is presented, with illustrative models motivated to (i) characterize local risk dependencies and influences over both spatial and temporal dimensions, (ii) model risk heterogeneities and discontinuities, and (iii) predict and forecast areal-level disease risks and occurrences. The broadened constructions allow rich options of intuitive parameterization for disease mapping and spatial regression. Illustrative parameterizations are presented for Bayesian hierarchical models of Poisson, zero-inflated Poisson, and Bernoulli data models, respectively. They are also discussed in the context of quantifying time-varying or time-invariant effects of (omitted) covariates, with application to prediction and forecasting areal-level COVID-19 infection occurrences and probabilities of zero-infection. The model constructions presented herein have much wider scope in offering a flexible framework for modelling complex spatiotemporal data and for estimation, learning, and forecasting purposes.

The new normal: a UK fertility clinic experience of universal RT-PCR SARS-CoV-2 testing.

Following the temporary closure of fertility clinics in 2020 in many countries across the world, the SARS-CoV-2 pandemic has meant that the sector has had to rapidly adapt to novel ways of operating. The aim of this study was to investigate the efficacy and feasibility of universal real-time polymerase chain reaction testing at an IVF clinic within a UK tertiary referral centre. Between March and December 2020, we performed 2,401 SARS-CoV-2 RT-PCR tests on 1,215 individual patients, of which eight were positive (0.3%). Appropriate positive case identification allowed for delay in treatment initiation or cancellation as applicable. This has allowed our unit to continue to operate safely and efficiently.

A phase 1, open-label, randomized drug-drug interaction study of zanubrutinib with moderate or strong CYP3A inhibitors in patients with B-cell malignancies.

BTK inhibitor exposure increases significantly when coadministered with CYP3A inhibitors, which may lead to dose-related toxicities. This study explored the pharmacokinetics, efficacy, and safety of zanubrutinib when coadministered with moderate or strong CYP3A inhibitors in 26 patients with relapsed or refractory B-cell malignancies. Coadministration of zanubrutinib (80 mg BID) with moderate CYP3A inhibitors fluconazole and diltiazem or zanubrutinib (80 mg QD) with strong CYP3A inhibitor voriconazole resulted in comparable exposures to zanubrutinib (320 mg QD) with AUC0-24h geometric least squares mean ratios approaching 1 (0.94, 0.81, and 0.83, for fluconazole, diltiazem, and voriconazole, respectively). The most common treatment-emergent adverse events were contusion (26.9%), back pain (19.2%), constipation and neutropenia (15.4% each), and rash, diarrhea, and fall (11.5% each). This study supports current United States Prescribing Information dose recommendations for the coadministration of reduced-dose zanubrutinib with moderate or strong CYP3A inhibitors and confirms the favorable efficacy and safety profile of zanubrutinib.

Revisiting Gaussian Markov random fields and Bayesian disease mapping.

We revisit several conditionally formulated Gaussian Markov random fields, known as the intrinsic conditional autoregressive model, the proper conditional autoregressive model, and the Leroux et al. conditional autoregressive model, as well as convolution models such as the well known Besag, York and Mollie model, its (adaptive) re-parameterization, and its scaled alternatives, for their roles of modelling underlying spatial risks in Bayesian disease mapping. Analytic and simulation studies, with graphic visualizations, and disease mapping case studies, present insights and critique on these models for their nature and capacities in characterizing spatial dependencies, local influences, and spatial covariance and correlation functions, and in facilitating stabilized and efficient posterior risk prediction and inference. It is illustrated that these models are Gaussian (Markov) random fields of different spatial dependence, local influence, and (covariance) correlation functions and can play different and complementary roles in Bayesian disease mapping applications.