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Background: There is limited literature assessing cosmetic lip size preferences in darker-skinned individuals. Objective: To measure preinjection lip augmentation preferences and postinjection satisfaction using the revised Lip Fullness Scale (LFS) in female participants with Fitzpatrick Skin Type V and VI. Methods: Females, aged 21 and over, with Fitzpatrick Skin Type V and VI desiring lip augmentation were recruited from a high-volume outpatient facial plastic surgery clinic. The LFS scale was administered pre- and postinjection. FACE-Q scales which measure patient reported outcomes for facial cosmetic procedures were administered postinjection. Results: Twenty-two female subjects participated in the study. The average age was 33.2 years (SD = 8.1). Fourteen participants (14) were Fitzpatrick V and eight (8) were Fitzpatrick VI. The average preinjection self-assessment LFS was 3.5. The final average postinjection self-assessment LFS score was 4.3. The increase in final postinjection LFS scores was found to be statistically significant with a p -value <0.001 when compared with preinjection LFS scores. Patients reported high satisfaction on postinjection FACE-Q. Conclusion: Patients with darker skin may prefer marked to very marked lip fullness, and physicians should be conscientious in understanding patients' individual perspectives and aesthetic goals.[Box: see text].

The bone is a highly dynamic organ that undergoes continuous remodeling through an intricate balance of bone formation and degradation. Hyperactivation of the bone-degrading cells, the osteoclasts (OCs), occurs in disease conditions and hormonal changes in females, resulting in osteoporosis, a disease characterized by altered microarchitecture of the bone tissue, and increased bone fragility. Thus, building robust assays to quantify OC resorptive activity to examine the molecular mechanisms underlying bone degradation is critical. Here, we establish an in vitro model to investigate the effect of estrogen withdrawal on OCs derived from the mouse macrophage RAW 264.7 cell line in a bone biomimetic microenvironment. This simple and robust model can also be adapted to examine the effect of drugs and genetic factors influencing OC resorptive activity in addition to being compatible with fluorescent imaging. Key features • A robust in vitro protocol that allows molecular and functional studies of mature osteoclasts in response to estrogen and its withdrawal. • Generation of inorganic bone-mimetic substrates for culturing and examining osteoclast resorptive behavior. • This quantitative image-based approach is compatible with brightfield and fluorescence microscopy to assess osteoclast resorptive activity., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2025 The Authors; This is an open access article under the CC BY-NC license.)

Purpose: 10-15% of prostate cancers (PCa) harbor recurrent FOXA1 aberrations whereby the alteration type and the effect on the forkhead( FKH) domain impacts protein-function. We developed a FOXA1 classification system to inform clinical management., Experimental Design: 5,014 PCa were examined using whole exome and transcriptome sequencing from the Caris database. We denoted class 1 FOXA1 alterations as missense and in-frame insertions/deletions with subclasses oriented with respect to the FKH domain: these were in the first part of the FKH domain (class 1A: amino acids [AA] 168-246), within the Wing2 region of FKH (class 1B: AA 247-269), or outside FKH (class 1C: AA 1-167, 270+). Two hotspot missense mutations at R219 were denoted class 2. Class 3 included predicted-truncating mutations with subclasses partitioned based on the FKH domain (class 3A: AA 1-269, class 3B: AA 270+). Class 4 represented FOXA1 amplifications. Real-world overall survival and therapy outcomes were determined from insurance claims., Results: FOXA1 alterations did not influence survival when considered in aggregate, but had distinct prognostic effects when stratified by class. Class 1A alterations were associated with overall improved survival (HR=0.57, p=0.03); a similar trend was seen with Class 1B (HR=0.88, p=0.07). Conversely, class 1C exhibited worse survival upon 2nd-generation androgen receptor signaling inhibitor (ARSI) treatment (HR=1.93, p<0.001). Class 2 mutations (R219C/S) were enriched in neuroendocrine prostate cancers and were associated with overall poor survival (HR=2.05, p<0.001) and worse outcomes to first-line androgen-deprivation therapies (HR=2.5, p<0.001). Class 3A alterations indicated improved survival (HR=0.70; p=0.01) whereas class 3B alterations portended poor outcomes (HR=1.50; p<0.001). Amplifications (class 4) indicated poor outcomes (HR=1.48; p=0.02). Molecularly, different FOXA1 alteration classes harbored distinct mutational and immunologic features as well as unique transcriptional programs. Finally, relative to European-Americans, African-Americans had increased class 1C alterations whereas Asian-Pacific patients had increased class 1B alterations., Conclusions: FOXA1alterations should not be interpreted in aggregate, as different classes are associated with divergent molecular features and clinical outcomes. Our revised classification schema facilitates clinical decision making for PCa patients and uncovers important racial differences.

Pharmacists across the United States are rapidly gaining the ability to bill the medical benefit, increasing their ability to optimally and sustainably contribute to patient care. Medical billing is the process by which a provider submits a claim for reimbursement to the medical insurance benefit based on services provided to a patient. As pharmacists lean into new and expanding opportunities related to medical billing, pharmacy educators must also prepare graduates who can explain the importance of and execute skills related to medical billing. Colleges and schools of pharmacy must take action now to improve curricula to ensure student readiness upon graduation. Tools and resources are under development to help support faculty in implementing this curricular change., Competing Interests: Declaration of Competing Interest The American Association of Colleges of Pharmacy is hosting “How to Teach Medical Billing Basics: A Hands-On Workshop” in November 2024. Shanna O’Connor and Jennifer Bacci will be presenters at the Workshop and Nidhi Gandhi-Patel and Miranda Steinkopf are planning and hosting the Workshop. The remaining authors have no competing interests to declare., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The author reports no conflicts of interest.

Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to report regarding the present study., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore., Methods: We will perform a prospective, multi-centre, type II hybrid effectiveness-implementation study with a post-design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train "genetic nephrologists" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes, steroid-resistant primary nephrotic syndrome, apparent familial IgA nephropathy, or chronic kidney disease with no apparent cause), and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease), and cost-effectiveness., Conclusion: This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process, and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: This study is an economic evaluation of total knee replacement (TKR) in comparison with non-surgical management in India., Methods: Cost-utility analysis and budget impact analysis (BIA) were conducted on individuals aged ≥ 50 years with osteoarthritis of the knee (OA knee) Kellgren-Lawrence grades 2 and 3 using a provider's perspective. Three scenarios were considered, varying the age at which TKR is administered while assuming a 20-year lifespan for the implant. A Markov model was used to determine incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted incorporating implant costs and other input parameters., Results: Net quality-adjusted life-years (QALYs) gained per OA knee treated with TKR were superior when performed at the age of 50, regardless of OA severity and across all scenarios. The lowest ICER was 36,107 Indian National Rupees (INR) (USD 482.9)/QALY gained, observed at 50 years, while the highest was INR 61,363 (USD 820.72)/QALY gained at 70 years for grade-2 severity. Sensitivity analysis revealed that the ICER was most sensitive to the cost of non-surgical management, health utility values gained in an improved state, and the cost of TKR across scenarios. For the BIA in Scenario 1, with 40% coverage for TKR, costs reach INR 5013 crores (cr) (USD 670,477,060) in 2023 and INR 8444 cr (USD 1,024,628,736) in 2028 (1% of government budgets). In Scenario 2 (full coverage), costs are INR 12,532 cr (USD 1,520,683,008) (2.7%) in 2023, declining to 2.4% in 2028. In Scenario 3, covering 40% under the National Health Mission (NHM), costs vary from 17% in 2023 to 25% in 2028., Conclusion: This study concludes that TKR is a cost-effective treatment option compared with non-surgical management for OA knee in India, irrespective of age, implant types, and severity., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article. Funding: This study was conducted by Regional Resource Hub-HTAIn and IIPH-Hyderabad which is funded by Department of Health Research under the Ministry of Health and Family Welfare (MoHFW), Government of India. Data availability statement: The data used in this study were extracted from literature and costs were extracted from the National Health System Cost Database for India (NHSCD). ( https://pgicostdatabase.co.in/ ) Code availability: The data analysis for this study was conducted using Microsoft Excel. The Excel files, including all relevant data sets and analysis formulas, are available as supplementary material. Author contributions: Conceptualization: Lipika Nanda, Ambarish Dutta, Sarit Kumar Rout; Methodology: Ambarish Dutta, Sarit Kumar Rout, Amatullah Sana Qadeer, Naline Gandhi, Ananda Meher; Formal analysis and investigation: Amatullah Sana Qadeer, Naline Gandhi, Ananda Meher, Abhilash Patra, Jennifer Rachel, Winnie Paulson; Writing—original draft preparation: Amatullah Sana Qadeer, Winnie Paulson, Ananda Meher, Ambarish Dutta; Writing—review and editing: Nirupama AY, Sarit Kumar Rout, Amatullah Sana Qadeer; Resources: Lipika Nanda; Supervision: Lipika Nanda. All authors have read and approved the final version of the manuscript. Ethics approval: Ethical approval for this study was obtained from Institutional Ethics Committee at Indian Institute of Public Health, Hyderabad, India (ID: IIPHH/TRCIEC/275/2020) Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

Olfactory neuroblastoma (ONB), sinonasal undifferentiated carcinoma (SNUC), and sinonasal neuroendocrine carcinoma (SNEC) are rare malignancies arising from the sinonasal tract with limited therapeutic options. The expression of the somatostatin receptor 2 gene ( SSTR2 ), which is expressed in other neuroendocrine neoplasms and is therapeutically actionable, has been reported in these tumors. Here, we analyzed SSTR2 gene expression and its associations with genomic features, established biomarkers predicting of immune response, and the tumor immune microenvironment in a cohort of ONB, SNUC, and SNEC tumor samples (26, 13, and 8 samples, respectively) from a real-world database. SSTR2 gene expression was high in neural-type ONB and low in basal-type ONB and in most of the SNUC and SNEC cases; there was no difference in expression between primary and metastatic tumors. The T cell-inflamed (TCI) score analysis classified 38.5% of SNUC cases as T cell-inflamed compared to only 3.9% of ONB and 0% of SNEC cases; 26.9% of ONB cases were classified as intermediate TCI; and SNEC had the lowest relative immune cell infiltration by deconvolution. In high SSTR2 -expressing ONB, there was a higher proportion of infiltrating of Natural Killer cells and dendritic cells by deconvolution. Additionally, high SSTR2 -expressing ONB was enriched for proliferation pathways, including E2F and Myc targets and G2M checkpoints. In conclusion, our findings delineate significant differences between these three types of sinonasal malignancies that were examined. In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.

Background: In patients with colorectal cancer (CRC), the therapeutic effects of conventional immune checkpoint inhibitors targeting the adaptive immune system are largely limited to those with microsatellite instability-high tumors. Meanwhile, new immunotherapies targeting the innate immune system are attracting increasing attention. CD47 is a representative innate immune checkpoint involved in the evasion of tumor cell phagocytosis by macrophages. This large-scale study comprehensively examined the molecular significance of CD47 gene expression in CRC., Methods: We analyzed the next-generation sequencing data of DNA and RNA from 14,287 CRC cases included in the data set of a commercial Clinical Laboratory Improvement Amendments-certified laboratory (Caris Life Sciences). The cases were divided into two groups based on the median value of CD47 gene expression levels. The molecular and immune profiles between the groups were compared, and the relationship between CD47 expression and survival outcomes was further examined., Results: In CD47 -high tumors, the proportion of consensus molecular subtypes 1 and 4 was significantly higher than in CD47 -low tumors. The expression levels of damage-associated molecular pattern-related genes showed a positive correlation with CD47 expression levels. Major oncogenic pathways, such as mitogen-activated protein kinase, phosphoinositide 3-kinase, angiogenesis, and transforming growth factor beta, were significantly activated in CD47 -high tumors. Additionally, the expression levels of a panel of adaptive immune checkpoint genes and estimates of immune cells constituting the tumor microenvironment (TME) were significantly higher in CD47 -high tumors., Conclusions: CD47 expression in CRC was associated with the activation of several oncogenic pathways and an immune-engaged TME. Our findings may provide valuable information for considering new therapeutic strategies targeting innate immune checkpoints in CRC., Competing Interests: Competing interests: NG, JX, and WMK are employees of Caris Life Sciences. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We have identified endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) as a poor prognostic indicator in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (EGFR MUT -NSCLC). In addition, comparison of high versus low ERO1A expression among cohorts of EGFR MUT -NSCLC primary samples revealed that ERO1A expression correlated with increased expression of proteins that regulate secretion. Using the CPTAC proteomic data set in lung adenocarcinoma we found that high ERO1A protein expression correlated with both extracellular matrix and matrix modifying enzymes. In this report, we found that ablating ERO1A expression was a determinant of clonogenicity, tumor sphere formation, spheroid growth and growth in vivo, as well as response to Osimertinib. We validated that ERO1A-knockout EGFR MUT -LUAD cell lines demonstrated a reduction in secretion of both laminin gamma 2 (LAMC2) and the collagen modifying enzyme lysyl oxidase-like 2 (LOXL2). Our work supports the role of ERO1A in modulating the tumor microenvironment that is likely to contribute to tumor progression., (© 2024. The Author(s).)

Introduction: Glycemic management in the intensive care unit is an evolving practice area. This evolution has included the refinement of blood glucose targets, matching glycemic management to premorbid status, and investigations into the impact of glycemic variability and relative hypoglycemia on ICU outcomes. The interplay between these phenomena and absolute hypoglycemia has yet to be investigated in hyperglycemic emergencies. Objectives: To examine the incidence of and risk factors for relative hypoglycemia and absolute hypoglycemia in patients admitted to an intensive care unit for the management of hyperglycemic emergencies. Methods: This was a retrospective, single-center, exploratory analysis of adults admitted to the medical intensive care unit for diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome. The primary outcome was the incidence of relative hypoglycemia, defined as a blood glucose level 30% lower than baseline. The baseline was determined by the estimated average blood glucose calculated from hemoglobin A1c within 3 months of index admission. Secondary outcomes were ICU length of stay, glycemic variability, and incidence of absolute hypoglycemia. Results: Relative hypoglycemia was observed in 60% of patients in the cohort. Longer insulin infusion duration and higher hemoglobin A1c levels were found to statistically increase the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU length of stay were associated with the risk of developing absolute hypoglycemia. Conclusions: Relative hypoglycemia is a frequent occurrence in this patient population. Hemoglobin A1c and duration of the insulin infusion statistically influenced the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU stay were significantly associated with developing absolute hypoglycemia. While relative hypoglycemia is common in hyperglycemic emergencies, the clinical impact remains uncertain and warrants additional investigation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objectives: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC., Materials and Methods: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher's exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable., Results: A total of 711 METex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in POT1 and BRCA2 were enriched, and amplifications in MDM2, HMGA2, CDK4, and MET were common in METex14+ tumors. TMB-high and TP53 mutated tumors were reduced in METex14+ independent of histology. KEAP1 (2.1 vs 14.7 %) and STK11 mutations (0.8 vs 17.1 %) were reduced only in METex14+ nSq (vs METex14+ Sq, q < 0.05). While the prevalence of PD-L1 high tumors was enriched in METex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq METex14+. B-cells and CD8+ T-cells (1.07-1.43-fold) were enriched in nSq METex14+, and dendritic cells (0.32 fold) were reduced only in METex14+ Sq. METex14+ tumors had a modest improvement in mOS compared to METex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, METex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. METex14+ nSq tumors were associated with improved mOS compared to METex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p < 0.0001)., Conclusion: METex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer Marks holds R&D authorship with Janssen Scientific Affairs. Nishant Gandhi, Joanne Xiu, Phillip Walker, and Matthew J. Oberley are employed by Caris Life Sciences. So Yeon Kim receives institutional grant funding from Boehringer Ingelheim, Astra Zeneca, Genentech, BMS, Loxo-Lilly, Genmab, and Dynamicure. Additionally, she has consulted for Amgen.Balazs Halmos receives institutional grant funding from Boehringer Ingelheim, Astra Zeneca, Merck, BMS, Advaxis, Amgen, AbbVie, Daiichi, Pfizer, GSK, Beigene, Janssen, Black Diamond Therapeutics, Forward Pharma, Numab, and Arrivent. He also serves on the Data Safety Monitoring Board/Advisory board for BMS, TPT, Apollomics, eFECTOR, and City of Hope. Melina E. Marmarelis reports research funding from Eli Lilly (Inst), AstraZeneca (Inst), Merck (Inst), Genentech (Inst), and holds a consulting role with Astra Zeneca, Novocure, Boehringer Ingelheim, Janssen, Takeda, Blueprint Pharmaceuticals, Bayer, Bristol Myers Squibb, Ikena, Regeneron. She also receives honorarium from Thermo Fisher and holds stock in Merck and Johnson & Johnson. Lyudmila Bazhenova reports a professional medical writing service funded by Mirati Therapeutics Inc, along with consulting roles with Pfizer, Genentech, Janssen, Novocure, Daiichi Sankyo, Anheart, BMS, Sanofi, Gilead, Teligene, Boehringer Ingelheim, Neuvogen, Bayer, BioAtla, Summit Therapeutics, Merck, Abbvie, Regeneron, Intervenn, Elevation Oncology, and Mirati. Additionally, she has institutional consulting with Takeda and Astra Zeneca, serves on the Data Safety Monitoring for ORIC Pharmaceuticals and Neuvogen, and holds stock in Epic Sciences. Stephen V. Liu holds a consulting role with AstraZeneca, Bristol-Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Novartis, Regeneron, Sanofi, and Takeda. He also receives research institutional grant funding from Alkermes, Bristol-Myers Squibb, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, Pfizer, RAPT, and Turning Point Therapeutics, and serves on the Data Safety Monitoring Board for Candel Therapeutics. The remaining authors have no relevant financial disclosures to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas. Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ∼0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors. Significance: The identification of targetable genomic subsets of cancer has revolutionized precision oncology and offers patients treatments with more selective and effective agents. Here, we demonstrate that activating, oncogenic MET tyrosine kinase domain mutations are found across a diversity of cancer types and are responsive to MET tyrosine kinase inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Workplace violence (WPV) in Emergency Departments (EDs) is an increasingly recognized challenge healthcare providers face in low-resource settings. While studies have highlighted the increased prevalence of WPV in healthcare, most of the existing research has been conducted in developed countries with established laws and repercussions for violence against healthcare providers. More data on WPV against ED providers practicing in low-resource settings is necessary to understand these providers' unique challenges., Objective: This study aims to gain insight into the incidence and characteristics of WPV among ED healthcare providers in India., Methods: This study was conducted at two EDs in geographically distinct regions of India. A survey was designed to assess violence in EDs among healthcare providers. Surveys were distributed to ED workplace providers, completed by hand, and returned anonymously. Data was entered and stored in the RedCAP database to facilitate analysis., Results: Two hundred surveys were completed by physicians, nurses, and paramedics in Indian EDs. Most reported events involved verbal abuse (68%), followed by physical abuse (26%), outside confrontation (17%), and stalking (5%). By far, the most common perpetrators of violence against healthcare workers were bystanders including patient family members or other accompanying individuals. Notably, reporting was limited, with most cases conveyed to ED or hospital administration., Conclusion: These results underscore the prevalence of WPV among Indian ED healthcare providers. High rates of verbal abuse followed by physical abuse are of concern. Most perpetrators of WPV against healthcare providers in this study were patient family members or bystanders rather than the patients themselves. It is imperative to prioritize implementing prevention strategies to create safer work environments for healthcare workers., (© 2024. The Author(s).)

Estrogen (17β-estradiol) deficiency post-menopause alters bone homeostasis whereby bone resorption by osteoclasts exceeds bone formation by osteoblasts, leading to osteoporosis in females. We established an in vitro model to examine the consequences of estrogen withdrawal (E2-WD) on osteoclasts derived from the mouse macrophage RAW 264.7 cell line and utilized it to investigate the mechanism behind the enhanced osteoclast activity post-menopause. We found that a greater population of osteoclasts that underwent E2-WD contained a podosome belt necessary for osteoclasts to adhere and resorb bone and possessed elevated resorptive activity compared to osteoclasts exposed to estrogen (E2) continuously. Our results show that compared to osteoclasts that received E2 continuously, those that underwent E2-WD had a faster rate of microtubule (MT) growth, reduced RhoA activation, and shorter podosome lifespan. Thus, altered podosome and MT dynamics induced by the withdrawal of estrogen supports podosome belt assembly/stability in osteoclasts, which may explain their enhanced bone resorption activity.

Background: To date, no intervention has definitively improved outcomes for families of critical illness survivors. An integrated perspective on caregivers' needs after critical illness could help identify high-priority intervention targets and improve outcomes., Objectives: To obtain diverse perspectives on the needs, barriers and facilitators, and social determinants of health associated with family caregiving across the critical illness continuum and assess the extent to which successful caregiving interventions in other populations may be adapted to the critical illness context., Methods: This qualitative content analysis of 31 semistructured interviews and 10 focus groups with family caregivers, health care providers, and health care administrators explored family caregivers' needs during post- intensive care unit (ICU) transitions and the barriers and facilitators associated with addressing them. Trained coders analyzed transcripts, identified patterns and categories among the codes, and generated themes., Results: Caregivers have 3 instrumental needs: formal and informal support, involvement in care planning, and education and training. Only caregivers described their self-care and mental health needs. Social determinants of health are the key barriers and facilitators shaping the caregivers' journey, and caregiving as a social determinant of health was a prominent theme., Conclusions: Caregivers have instrumental, self-care, and mental health needs after critical illness. Adapting hands-on and skills training interventions to the post-ICU setting, while tailoring interventions to caregivers' health-related social context, may improve caregiver outcomes., (©2024 American Association of Critical-Care Nurses.)

Membranous nephropathy (MN) is an autoimmune condition that is a common cause of nephrotic syndrome in nondiabetic adults. In this study, we highlight a case of a 22-year-old male with a past medical history of arthrogryposis multiplex congenita (AMC) who initially presented with right flank pain and hematuria. Subsequent workup revealed significant proteinuria with biopsy-proven primary MN. Early detection of the disease is critical to establish treatment promptly and prevent complications such as those resulting from a hypercoagulable state., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Agrawal et al.)

Primary human hepatocytes (PHHs) are used extensively for in vitro liver cultures to study hepatic functions. However, limited availability and invasive retrieval prevent their widespread use. Induced pluripotent stem cells exhibit significant potential since they can be obtained non-invasively and differentiated into hepatic lineages, such as hepatocyte-like cells (iHLCs). However, there are concerns about their fetal phenotypic characteristics and their hepatic functions compared to PHHs in culture. Therefore, we performed an RNA-sequencing (RNA-seq) analysis to understand pathways that are either up- or downregulated in each cell type. Analysis of the RNA-seq data showed an upregulation in the bile secretion pathway where genes such as AQP9 and UGT1A1 were higher expressed in PHHs compared to iHLCs by 455- and 15-fold, respectively. Upon immunostaining, bile canaliculi were shown to be present in PHHs. The TCA cycle in PHHs was upregulated compared to iHLCs. Cellular analysis showed a 2-2.5-fold increase in normalized urea production in PHHs compared to iHLCs. In addition, drug metabolism pathways, including cytochrome P450 (CYP450) and UDP-glucuronosyltransferase enzymes, were upregulated in PHHs compared to iHLCs. Of note, CYP2E1 gene expression was significantly higher (21,810-fold) in PHHs. Acetaminophen and ethanol were administered to PHH and iHLC cultures to investigate differences in biotransformation. CYP450 activity of baseline and toxicant-treated samples was significantly higher in PHHs compared to iHLCs. Our analysis revealed that iHLCs have substantial differences from PHHs in critical hepatic functions. These results have highlighted the differences in gene expression and hepatic functions between PHHs and iHLCs to motivate future investigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Sponsored by the American Association of Colleges of Pharmacy (AACP), the New Investigator Award (NIA) provides start-up funding for the independent research programs of early-career faculty. However, there is limited information on outcomes. Thus, the objective was to determine the impact of the NIA program on the stimulation of recipient research programs and AACP involvement., Methods: A cross-sectional survey of 2012-2022 NIA Award recipients and current pharmacy Department Chairs was conducted. The instruments (NIA Recipient:28-items, Chair:15-items) were administered via Qualtrics with data reported descriptively., Results: Responses were received from 96 NIA recipients and 157 Chairs (60%, 49% response rate). From the NIA recipients, most respondents received the award within their first 2 years of appointment (59%), received it on the first submission (61%), remained in academia (96%) at the same institution (90%), and were AACP members (80%) with a variety of involvement. Projects were typically completed (81%) and utilized for another grant (51%). Two-thirds of faculty had received external funding post-NIA (64%), and most felt the grant was valuable or very valuable. From the Department Chair survey, 40% had NIA recipients and 13% had served as a mentor. Departments did not have an NIA development/review process (77%) but had a mentoring program (59%). Most perceived the NIA program to be valuable/very valuable., Conclusion: Overall, chairs and NIA recipients have positive perceptions of the value of the NIA and recipients reported evidence of scholarly success., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We outline the presentation of a 68-year-old woman who received a chest radiograph due to her insurance requirements, resulting in the discovery of a left-sided pleural effusion. The effusion was further characterized as loculated on subsequent imaging. Thoracentesis yielded exudative fluid, leading to the patient undergoing video-assisted thoracoscopic surgery (VATS). During this procedure, a cystic mass was visualized, with the conversion of the operation to an open thoracotomy and left lower lobe lobectomy. Pathology was positive for spindle cell sarcoma. A thorough history of the patient revealed a decades-long occupational exposure to asbestos. The significance of this report is to illustrate the clinical presentation, immunohistochemical characteristics, and management of a rare spindle cell malignancy. Our case also raises the importance of screening patients on an individualized, shared decision-making basis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Walker et al.)

BACKGROUND Three driver mutations have been identified in patients with essential thrombocythemia - JAK2 V617F, CALR, and MPL. Out of these, JAK2 V617F is mostly common. These mutations are thought to be mutually exclusive; therefore, the initial workup may not include the identification of all mutations separately. CASE REPORT We present a case of a 55-year-old woman who was referred to the hematology clinic for an elevated platelet count noted when she was hospitalized for a renal stone. The patient was asymptomatic. A workup was initiated for essential thrombocythemia, and she was tested for JAK2 V617F mutation using an allele-specific polymerase chain reaction (AS-PCR) test in peripheral blood, which came back positive. The variant allele frequency was 2%. She underwent a bone marrow biopsy, and next-generation sequencing (NGS) showed a CALR mutation. A 52 bp deletion-type mutation was detected in the CALR gene on exon 9, with a variant allele frequency of 7%. The NGS did not detect JAK2 mutation due to its low sensitivity. She was started on aspirin alone as she was less than 60 years old and had no history of thrombotic events. The patient has been following up with the hematology clinic for the last 2 years and has not had any thrombotic events. CONCLUSIONS We propose that in patients with a low JAK2 V617 allele variant, testing for other driver mutations should be performed. In our patient, JAK2 mutation could be clonal hematopoiesis of indeterminate potential; therefore, the dominant mutation (CALR) would determine the disease phenotype.

Rapid industrialization and agricultural development have resulted in the accumulation of a variety of harmful contaminants in water resources. Thus, various approaches such as adsorption, photocatalytic degradation and methods for sensing water contaminants have been developed to solve the problem of water pollution. Metal-organic frameworks (MOFs) are a class of coordination networks comprising organic-inorganic hybrid porous materials having organic ligands attached to inorganic metal ions/clusters via coordination bonds. MOFs represent an emerging class of materials for application in water remediation owing to their versatile structural and chemical characteristics, such as well-ordered porous structures, large specific surface area, structural diversity, and tunable sites. The present review is focused on recent advances in various MOFs for application in water remediation via the adsorption and photocatalytic degradation of water contaminants. The sensing of water pollutants using MOFs via different approaches, such as luminescence, electrochemical, colorimetric, and surface-enhanced Raman spectroscopic techniques, is also discussed. The high porosity and chemical tunability of MOFs are the main driving forces for their widespread applications, which have huge potential for their commercial use., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To demonstrate the effects of PDO threads non-surgical rhinoplasty on patients' quality of life (using FACE-Q Scale) and first impression assessments., Methods: This is a prospective cohort study of 10 adult patients who sought non surgical rhinoplasty to improve tip rotation or reduce the appearance of a dorsal hump. All patients fulfilled the study's enrollment criteria. Prior to treatment, patients completed pre-treatment FACE-Q surveys and pre-treatment photos were obtained. Each patient was treated with the appropriate size and number of PDO threads necessary to achieve optimal correction result (OCR). Two weeks after treatment, the patient completed posttreatment FACE-Q surveys and posttreatment photos were obtained and analyzed. First impression surveys were created using pre- and posttreatment photos, and the survey was completed by 146 blinded evaluators., Results: There was statistically significant improvement in the FACE-Q scores for social function (p = 0.02), psychological function (p = 0.0009) and satisfaction with nose (p = 0.0001). There was significant reduction in scores for appearance related psychosocial distress (p = 0.03). For the first impression surveys, there was a statistically significant improvement (p = 0.029) in the attractiveness scale posttreatment. Although not statistically significant, there was reduction of the dorsal hump (p = 0.15) and increase in the nasolabial angle (p = 0.48) and Goode's ratio (p = 0.16). There were no major adverse events or complications., Conclusion: This study shows that the PDO threads alone can be used safely to achieve minor nasal changes especially in tip rotation and appearance of dorsal hump, to improve patients' quality of life, and perceived attractiveness of treated patients., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Aim: This research aimed to assess and compare the translucency and mechanical properties of partially stabilized zirconia in contrast to lithium disilicate, particularly within the context of translucent zirconia., Settings and Design: The experimental design entails examining fifty samples, with ten drawn from each of the five distinct categories of ceramic materials, as part of this in vitro study. Translucency is measured using the Konica Minolta CM-3600D spectrophotometer, assessing Delta E through Lab values against white and black backgrounds. Flexural strength is analyzed via a 3-point bend test on a universal testing machine, with a controlled crosshead speed set at 1 mm/min., Materials and Methods: The study included the five categories of ceramic materials, each consisting of ten samples: High-strength zirconia (Katana HT), translucent zirconia (e.max Zircad MT and Cercon ht ML), and lithium disilicate (Press MT and LT). The Konica Minolta CM-3600D spectrophotometer is utilized to measure the translucency parameter. This involves determining the color difference (Delta E) by comparing the L*a*b values against both white and black backgrounds. The flexural strength (FS) of zirconia and lithium disilicate materials was analyzed through a 3-point bend test, aiming to compare their respective strengths. The testing procedure was carried out on a universal testing machine with a controlled crosshead speed set at 1 mm/min. The FS was calculated using the formula σ = FL/πR3 for circular disks, where σ represents the FS, F is the fracture load, L is the span length in millimeters, and R is the radius of the disk., Statistical Analysis Used: The Student's t-test was employed for statistical analysis., Results: The mean translucency parameter for e.max Press MT (6.33 ± 1.05) was significantly greater than all the specimens investigated. The Cercon ht ML exhibited a slightly higher translucency (2.18 ± 0.52) compared to e.max Zircad MT (1.49 ± 0.69), with a statistically significant difference (P = 0.022). Conversely, the FS of e.max Zircad MT (26.97 ± 2.06) was significantly greater (P < 0.001) than that of Cercon ht ML (23.25 ± 2.36). Notably, the Katana HT material demonstrated the highest load strength (32.92 ± 3.10), a statistically significant difference compared to its counterparts (P < 0.001)., Conclusions: Among the materials tested, lithium disilicate ceramics exhibited the highest translucency, with its MT variant demonstrating the lowest strength. Katana HT displayed significantly greater biaxial FS compared to translucent zirconia, surpassing even lithium disilicate. Translucent zirconia proved to be notably more translucent than high-strength zirconia. Within the category of translucent zirconia, e.max Zircad MT exhibited substantially higher FS than Cercon., (Copyright © 2024 Copyright: © 2024 The Journal of Indian Prosthodontic Society.)

Aim: The aim of this within-subject prospective clinical study was to investigate the scope of single implant mandibular overdenture by assessing its masticatory efficiency, clinical performance, and patient satisfaction compared to conventional complete dentures., Settings and Design: Prospective In Vivo Study., Material and Methods: This prospective in vivo study was conducted in the Department of Prosthodontics and Crown and Bridge, Christian Dental College, Ludhiana. A total of 12 completely edentulous patients received a single implant in the mandibular anterior midline region. After the healing period, the conventional maxillary and mandibular dentures were fabricated. 15 days post insertion of the conventional dentures, patients were evaluated for masticatory efficiency, clinical performance including retention and stability, and patient satisfaction. To evaluate the masticatory efficiency blue raspberry and original pink "Hubba Bubba tape gum" were used as a test food. Colorimetric analysis was done to assess variance of hue. To assess clinical performance, retention, and stability of the mandibular denture was recorded using a digital force gauge and was tabulated as per CU-modified Kapur's criteria. OHIP-14 index was used to assess patient satisfaction. After evaluation of the parameters of conventional dentures, the denture was converted into an implant-retained mandibular denture by chairside conversion with locator attachments. 15 days post-implant loading, parameters of the implant retained mandibular overdenture were assessed again followed by statistical analysis., Statistical Analysis Used: The masticatory efficiency was assessed using a paired t-test. The patient satisfaction was sequentially assessed with Wilcoxon signed rank test and thereafter paired t-test was used to compare between conventional complete denture and overdenture. Clinical performance was assessed using the Wilcoxon signed rank test., Results: The masticatory efficiency of single implant mandibular overdenture was higher than that of conventional complete dentures. The clinical performance of the overdenture was higher than that of the conventional denture. Stability being a time-dependent parameter might need longer follow-ups for further conclusions. Patient satisfaction with single implant retained overdenture was significantly higher than conventional complete dentures., Conclusion: Single implant mandibular overdenture has improved masticatory efficiency, clinical performance, and patient satisfaction compared to conventional complete dentures., (Copyright © 2024 Copyright: © 2024 The Journal of Indian Prosthodontic Society.)

Statement of Problem: The development of digital dental technologies has enabled clinicians to use additive and subtractive manufacturing techniques to fabricate interim restorations. However, knowledge of the trueness and precision of such restorations fabricated using digital light processing (DLP) and computer-aided design and computer-aided manufacturing (CAD-CAM) methods is limited., Purpose: The purpose of this in vitro study was to assess and compare the accuracy of interim crowns fabricated using DLP and CAD-CAM methods., Material and Methods: A typodont mandibular first molar was prepared for a ceramic crown, and a digital scan (Medit T500) was obtained to design interim crowns by using the CAD software program. The CAD data were designated as the reference data. A total of 20 crowns were fabricated by DLP and CAD-CAM technology. The fabricated interim crowns were further scanned using a laboratory scanner and were superimposed with the CAD data by using a 3-dimensional (3D) point cloud assessing software program (CloudCompare) for the evaluation of trueness and precision. Root mean square values (RMS) were obtained for the evaluation of discrepancies. The Student t test was used to compare data as the Shapiro-Wilk test confirmed the normal distribution., Results: RMS values for the trueness values of the external and intaglio surfaces of the 3D printed and milled interim crown displayed no statistically significant differences (P>.05). Precision for the external surface reported significance (P<.05), whereas that for the intaglio surface reported no significance (P>.05)., Conclusions: The accuracy of interim crowns fabricated by using DLP was comparable with that of milled crowns. Both manufacturing systems produced a true reproduction of the CAD. As for precision, the external surface of the DLP interim crown was statistically different from that of the milled group as it relates to the CAD., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Statement of Problem: Quad zygomatic implants have been used as a treatment option for patients with a severely resorbed maxilla. However, data on the average rate of success of the prosthesis, survival of the zygomatic implants, and associated complications are sparse., Purpose: The purpose of this systematic review and meta-analysis was to assess prosthetic and zygomatic implant success of treating severe maxillary resorption with prostheses supported by 4 zygomatic implants, with an additional review on potential complications., Material and Methods: A comprehensive search of studies published in English between January 2001 and December 2020 was performed in the PubMed, OVID, EBSCO, and EMBASE databases according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021219468). The population, intervention, comparison, and outcome (PICO) question was "What is the effectiveness of oral rehabilitations using only 4 zygomatic implants placed in severely resorbed maxillae?" The search results were subjected to a systematic review for articles reporting prosthetic success and zygomatic implant survival. Prosthetic success was analyzed by using a fixed-effects inverse-variance model. The random-effects model was adopted for meta-analysis as moderate heterogeneity was identified among studies that reported implant survival in quad zygoma treatments. The quality of publications was appraised by using the Critical Appraisal Skills Program (CASP) checklists., Results: Of the 82 titles, 7 studies that met the inclusion criteria without an overlap of patient cohorts were quantitatively analyzed for the average rate of prosthetic success and implant survival. All prostheses in the aggregated studies were immediately loaded with acrylic resin interim prostheses replaced by a definitive prosthesis, which consisted of overdentures retained by bar splinting (n=2), metal bar-reinforced prostheses (n=2), fixed screw-retained acrylic resin prostheses (n=34), and screw-retained titanium prostheses with ceramic or acrylic resin teeth (n=75). Technical complications of zygomatic implants included mobility associated with a machined surface and fracture of the abutment screw. The most common prosthetic complications reported were fracture of the definitive prosthesis and loss of the interim prosthesis subsequent to the failure of at least 1 zygomatic implant. The results showed that prostheses supported by quad zygoma implants displayed an overall success of 100% (CI=95%, I 2 =0.00%, P=.850), whereas zygomatic implants showed a survival rate of 98% (CI=95%, I 2 =60.48%, P=.040) with minimal implant failures and few complications., Conclusions: Although the data analysis showed favorable results for rehabilitating severely resorbed maxillae by using quad zygoma with high prosthetic success and high implant survival rate, further long-term clinical studies are required to strengthen the evidence. However, potential implant and prosthetic complications should be considered while planning this treatment approach., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Cotton ( Gossypium spp.) is the primary source of natural textile fiber in the U.S. and a major crop in the Southeastern U.S. Despite constant efforts to increase the cotton fiber yield, the yield gain has stagnated. Therefore, we undertook a novel approach to improve the cotton fiber yield by altering its growth habit from perennial to annual. In this effort, we identified genotypes with high-expression alleles of five floral induction and meristem identity genes ( FT , SOC1 , FUL , LFY , and AP1 ) from an Upland cotton mini-core collection and crossed them in various combinations to develop cotton lines with annual growth habit, optimal flowering time, and enhanced productivity. To facilitate the characterization of genotypes with the desired combinations of stacked alleles, we identified molecular markers associated with the gene expression traits via genome-wide association analysis using a 63 K SNP Array. Over 14,500 SNPs showed polymorphism and were used for association analysis. A total of 396 markers showed associations with expression traits. Of these 396 markers, 159 were mapped to genes, 50 to untranslated regions, and 187 to random genomic regions. Biased genomic distribution of associated markers was observed where more trait-associated markers mapped to the cotton D sub-genome. Many quantitative trait loci coincided at specific genomic regions. This observation has implications as these traits could be bred together. The analysis also allowed the identification of candidate regulators of the expression patterns of these floral induction and meristem identity genes whose functions will be validated.

Background: Fractional carbon dioxide (CO 2 ) laser resurfacing is used successfully for facial rejuvenation. Post procedure skincare is a variable that influences downtime caused by pain/tenderness, erythema, crusting, and bruising., Aims: The primary objective of this pilot study was to demonstrate the benefits of human platelet extract (HPE) (plated)™ CALM Serum, a new topical cosmetic product, following fractionated CO 2 ablative laser resurfacing treatment to the entire face versus standard of care., Methods: In a single-center, randomized, evaluator-blinded pilot study, a total of 18 subjects were randomized into two groups, CO 2 facial resurfacing followed by post-procedural standard of care (Stratacel silicone gel) or CO 2 facial resurfacing with the addition of HPE renewosomes in the CALM Serum., Results: CALM Serum demonstrated statistically significant less crusting at Day 10 compared to the control group (p = 0.0193) with less downtime in the first 14 days (p = 0.03). Subjects treated with CALM Serum had statistically significant brighter appearing skin at 14 days (p = 0.007) and more youthful looking skin on Days 14 and 30 (p = 0.003 and 0.04, respectively)., Conclusions: This study demonstrates that Renewosome™ technology provides statistically significant post-laser clinical recovery over silicone gel for reducing crusting, and downtime. Subjects reported less diary days of symptoms of pain/tenderness, redness, crusting/flaking, bruising, and itching in the first 14 days compared to the control group. CALM also demonstrated statistically significant improvements in brighter and more youthful appearing skin. CALM is safe and well tolerated., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objectives: The main objective of this review is to summarize the evidence on the core modelling specifications and methodology on the cost-effectiveness of TKR compared to non-surgical management. Another objective of this study is to synthesize evidence of TKR cost and compare it across countries using purchasing power parity (PPP)., Methodology: The electronic databases used for this review were MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), HTAIn repository, Cost effectiveness Analysis (CEA) registry, and Google Scholar. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) was used to assess the validity of the methods and transparency in reporting the results. The Quality of Health Economic Studies (QHES) was used to check the quality of economic evaluation models of the studies included. The cost of TKR surgery from high income and low- or middle-income countries were extracted and converted to single USD ($) using purchasing power parities (PPP) method., Result: Thirty-two studies were included in this review, out of which eight studies used Markov model, five used regression model, one each reported Marginal structure model, discrete simulation model, decision tree and Osteoarthritis Policy Model (OAPol) respectively to assess the cost-effectiveness of TKR. For PPP, twenty-six studies were included in the analysis of TKR cost. The average cost of TKR surgery was the lowest in developing country-India ($3457) and highest in USA ($19568)., Conclusion: The findings of this review showed that the Markov model was most widely used in the analysis of the cost effectiveness of TKR. Our review also concluded that the cost of TKR was higher in the developed countries as compared to the developing countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gandhi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Statement of Problem: Scientometrics is the study of measuring and analyzing scholarly literature. Scientometric analysis to determine the impact of prosthodontic journals on scientific contributions is lacking., Purpose: The purpose of this analysis was to compare the quality of prosthodontic journals based on performance indicators over 10 years (2010 to 2019)., Material and Methods: The SCImago Journal and Country Rank portal was used to identify various prosthodontic journals under the subject of dentistry. Seven journals publishing in the English language with "Prosthetics" and "Prosthodontics" in the title were identified and analyzed. The statistical analyses of the scientometric indicators for the 7 highest-ranked journals were performed with 1-way analysis of variance (ANOVA) and the Tukey post hoc tests (α=.05)., Results: The absolute SCImago journal rank (SJR) was highest at various time periods for the Journal of Prosthetic Dentistry (JPD), International Journal of Prosthodontics (IJP), and Journal of Prosthodontic Research (JPR). The JPD and IJP scored higher SJR than other journals during this period (P<.05). The mean cites per document and the h-index were highest for JPD (P<.05)., Conclusions: Scientometric tools enable the evaluation of journal performance to aid researchers when choosing a journal to which to submit their work. Analysis of the 7 prosthodontic journals revealed the performance of various journals and gives an insight into the journal characteristics for future researchers who wish to submit their scholarly work., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The role of immune checkpoint inhibitors (ICIs) continues to receive more attention as evidence emerges of their efficacy and improved survival in patients with advanced biliary tract malignancies including cholangiocarcinoma (CCA). In line with this evidence, we describe the case of a 52-year-old male patient who presented initially in October 2019 with abdominal pain. Investigations revealed multifocal hepatic masses that proved to be CCA that was considered unresectable. Chemotherapy with cisplatin (C) and gemcitabine (G) was initiated. In January 2020, progressive disease was noted, prompting the initiation of 5-fluorouracil (5-FU) and oxaliplatin along with pembrolizumab. Since March 2020, pembrolizumab monotherapy was pursued with radiological evidence of excellent response. Pembrolizumab monotherapy was continued through August 2022, where positron emission tomography (PET)/CT scan showed no evidence of active disease. This case serves to supplement the ongoing evidence of ICI efficacy especially as a durable, sustained radiological response was evident for more than three years from the time of diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Habib et al.)

Migraines, a chronic disease, can be debilitating in university students, affecting their academic performance, attendance, and social interactions. The purpose of this study was to identify the impact of COVID-19 on the role functioning and perceived stress levels of students suffering from migraine-like headaches., Methods: Two identical cross-sectional surveys were sent to students in Fall 2019 and Spring 2021 at a mid-sized university in the U.S. The students were queried on the headache impact scale (HIT-6) and perceived stress scale (PSS-10). Associations between the migraine-like headaches, severity of the headaches, stress levels, and headache impacts on the individuals' role functioning were analyzed., Results: The average age of the respondents (n = 721) was 20.81 ± 4.32 years in 2019 and (n = 520) 20.95 ± 3.19 years in 2021. A difference ( p = 0.044) was found in the HIT-6 score <49 category. The other categories of the HIT-6 and the PSS-10 were not significant., Conclusions: During COVID-19, more students answered that their migraine-like headaches had lower impacts on their role functioning, thus suggesting that the students were having less severe migraines. A trend was seen for student's stress levels, indicating a decrease from 2019 to 2021. Furthermore, our results showed that the impact of headaches and stress levels slightly declined throughout the pandemic.

Hypereosinophilic syndrome (HES) is a spectrum of diseases characterised by an elevated eosinophilic count causing end-organ damage. Differential diagnoses of hypereosinophilia are vast and include drug hypersensitivities, allergies, infections, cancers, autoimmune disorders and rare eosinophilic syndromes. Herein, we describe a case of a patient presenting with gastrointestinal (GI) symptoms including progressive dysphagia, abdominal distension, vomiting, diarrhoea and abdominal pain with significant peripheral eosinophilia who was found to have an overlap HES involving the GI tract. This patient's eosinophilia was rapidly corrected with intravenous methylprednisolone, and the patient experienced gradual resolution of clinical symptoms with maintenance oral prednisone. Due to the rarity and diverse presentation of HES, there are few large, longitudinal studies that describe disease progression and inform treatment guidelines. This case demonstrates the difficulty in designing a treatment regimen for these patients and emphasises the clinical need for improved understanding of HES., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Statement of Problem: Stresses applied to zygomatic implants have been determined to be transferred mainly to the zygomatic bone; however, consensus regarding the stress distribution pattern in the bone surrounding zygomatic implants has not yet been reached., Purpose: The purpose of this 3-dimensional (3D) finite element analysis (FEA) study was to visually compare the stress distribution pattern in 2 different zygomatic implant treatment modalities and evaluate the effect of masseter musculature involvement., Material and Methods: A 3D FEA craniofacial model was constructed from the computed tomography (CT) data of a selected patient with a severely atrophic edentulous maxilla. Modeled zygomatic and conventional implants were inserted into the craniofacial model supporting a prosthesis superstructure. Two types of treatment were considered in the study: 2 zygomatic implants placed bilaterally or 2 zygomatic implants placed in conjunction with at least 2 conventional implants at the anterior maxilla. The models were loaded with a vertical force of 150 N, a lateral force of 50 N, and a distributed occlusal force of 300 N applied to the insertion area of the masseter muscle. The stresses on and deformations of the bones and implants were then observed and compared with and without the involvement of the musculature component., Results: The stresses were distributed efficiently along the vertical and horizontal facial buttresses, as in the dentate skull; however, a difference in distribution pattern was observed when the models were loaded without applying the muscle component. The maximum deformation of bones surrounding the implants occurred in the abutment connection of the conventional anterior implant in the model with an additional conventional anterior implant., Conclusions: The FEA revealed the stresses were distributed efficiently along the vertical and horizontal facial buttresses, as in the dentate skull. However, the stresses in both models were concentrated in the zygomatic bone when incorporating the muscle component. Therefore, incorporating muscular force into FEA studies could affect the analysis result., (Copyright © 2023 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Aims: Spatially-organized increases in cytosolic Ca 2+ within pancreatic beta cells in the pancreatic islet underlie the stimulation of insulin secretion by high glucose. Recent data have revealed the existence of subpopulations of beta cells including "leaders" which initiate Ca 2+ waves. Whether leader cells possess unique molecular features, or localisation, is unknown., Main Methods: High speed confocal Ca 2+ imaging was used to identify leader cells and connectivity analysis, running under MATLAB and Python, to identify highly connected "hub" cells. To explore transcriptomic differences between beta cell sub-groups, individual leaders or followers were labelled by photo-activation of the cryptic fluorescent protein PA-mCherry and subjected to single cell RNA sequencing ("Flash-Seq")., Key Findings: Distinct Ca 2+ wave types were identified in individual islets, with leader cells present in 73 % (28 of 38 islets imaged). Scale-free, power law-adherent behaviour was also observed in 29 % of islets, though "hub" cells in these islets did not overlap with leaders. Transcripts differentially expressed (295; padj < 0.05) between leader and follower cells included genes involved in cilium biogenesis and transcriptional regulation. Providing some support for these findings, ADCY6 immunoreactivity tended to be higher in leader than follower cells, whereas cilia number and length tended to be lower in the former. Finally, leader cells were located significantly closer to delta, but not alpha, cells in Euclidian space than were follower cells., Significance: The existence of both a discrete transcriptome and unique localisation implies a role for these features in defining the specialized function of leaders. These data also raise the possibility that localised signalling between delta and leader cells contributes to the initiation and propagation of islet Ca 2+ waves., Competing Interests: Declaration of competing interest GR has received grant funding from, and is a consultant for, Sun Pharmaceuticals Inc. This company was not involved in the present study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) and anemia are both prevalent in India. Glycated hemoglobin (HbA1c) is the gold standard test for the diagnosis of DM and monitoring of glycemic status. Hemoglobin (Hb) being the integral component of HbA1c, there is a possibility that anemia can also affect the level of HbA1c apart from the various other factorsObjectives: To study the prevalence, type of anemia, and correlation between HbA1c and anemia, including red blood cell (RBC) indices in euglycemic type 2 DM patients. The study was conducted with the objective of studying the correlation between HbA1c and anemia in euglycemic diabetic patients having controlled blood glucose over a period of 3 monthsMethodology: This cross-sectional study was conducted between May 2020 and May 2021 at the Department of General Medicine, Government Medical College, Kota, Rajasthan, India. All euglycemic diabetic patients with controlled blood glucose over a period of 3 months attending the outpatient department and fulfilling inclusion and exclusion criteria were enrolled in the studyInclusion criteria: All euglycemic type 2 DM patients with controlled blood glucose having three consecutive normal blood glucose levels [fasting blood sugar (FBS)-80-130 mg/dL and postprandial blood sugar (PP2BS) test-&lt;180 mg/dL] over a period of 3 months from the outpatient departmentExclusion criteria: Type 1 DM and latent autoimmune diabetes of adults, patients with hemolytic anemia, pregnancy, chronic alcoholism, chronic kidney disease, chronic liver disease, combined deficiency anemia, patients with increased FBS and PP2BS, acute and chronic inflammatory state, malignancy, anemia of chronic disease, and vitamin B12 deficiency were excluded from our studyDetailed investigations of diabetes and anemia were conducted. The effect of anemia on HbA1c was assessed, and the correlation of anemia with mean HbA1c was analyzed statistically Results: The prevalence of anemia in diabetic patients is 56.8%. Normocytic normochromic anemia is the most common, which was observed among 48.86% of diabetic patients. The median HbA1c of anemic patients is higher than nonanemic patients (p &lt; 0.01). There is a negative correlation between Hb and HbA1c (p &lt; 0.01). The correlation of RBC indices, that is, mean corpuscular Hb (MCH), mean corpuscular volume (MCV), and MCH with HbA1c, is also negative (p &lt; 0.01). There is a negative correlation between HbA1c and serum ferritin level, as indicated by the Pearson correlation test (p-value of &lt;0.01)Conclusion: Anemia is prevalent in type 2 DM patients without renal involvement, and also normocytic normochromic type is the most common, followed by iron deficiency anemia (IDA). HbA1c levels are significantly affected by the presence of moderate anemia in spite of controlled glycemia., (© Journal of the Association of Physicians of India 2011.)

Aim: To evaluate the flipped classroom model for teaching horizontal strabismus didactics in an ophthalmology residency program in China as part of a visiting professorship from the United States., Methods: Residents from an ophthalmology residency program in China were invited to participate in flipped classroom sessions taught by an experienced American ophthalmology faculty in 2018. Residents were instructed to watch a pre-class video lecture prior to the in-class-case-based activity. Content tests (5 Ophthalmic Knowledge Assessment Program style questions) and surveys were administered before and after the classroom sessions (100% response rate). These results were compared to that of an American cohort who were taught the same content., Results: The Chinese cohort of 12 residents preferred the flipped classroom to the traditional classroom at higher rates than the American cohort of 40 residents (92% vs 55%, P =0.04) and felt that all ophthalmology topics would be appropriate for the flipped classroom teaching style ( P -values between 0.008 and <0.001). In both Chinese and American cohorts, we found that the exotropia curriculum saw a small but significant improvement in performance following the flipped classroom session ( P =0.025 for Chinese residents; P =0.001 for US residents), whereas scores in both groups for the esotropia course did not significantly improve., Conclusion: This is the first study to evaluate the flipped classroom model implemented by a visiting ophthalmology professor in a global outreach setting. The flipped classroom sessions are viewed favorably by the Chinese residents relative to the US cohort with a modest impact on knowledge. Decreased in-person interpreter requirement and increased student engagement make this model valuable in cross-cultural visiting professorship settings. Finally, the flipped classroom may lend itself well to a virtual format to prevent the transmission of COVID-19, although such a format requires further study., (International Journal of Ophthalmology Press.)

Objective: To evaluate the effect of mask wearing on facial attractiveness and projected first impressions during the COVID-19 pandemic., Methods: A total of eight models were evaluated by 200 live raters and 750 online raters both with and without masks while smiling maximally. Both live and online raters looked at the models for 15 s, then completed a first impressions questionnaire., Results: Overall ratings for attractiveness were higher for both masked and unmasked conditions in-person versus online. Males were perceived more favorably both in impressions and attractiveness online when masked, whereas in person they were more favorable when unmasked. Females were perceived more favorably in impressions when unmasked both online and in person, but their attractiveness rating was higher when masked both online and in person. Regardless of gender and masking state, all first impressions were more favorable in person versus online. The differences were statistically significant (all p < 0.05)., Conclusions: Face masks have different effects for males versus females in both an online and in-person setting. Men are perceived more positively in-person when they smile unmasked while they are better ranked online when they smile masked. Females are better perceived in all domains other than attractiveness when smiling unmasked both online and in person. To optimize first impressions, individuals should seek to meet in person whenever possible when forming new relationships., (© 2022 Wiley Periodicals LLC.)

Background: The efficacy of 2% lignocaine is reduced in a hot tooth. Local aesthetic agents can be preheated and buffered to increase their effectiveness. The present investigation was carried out due to limited information concerning adult patients with symptomatic irreversible pulpitis in mandibular teeth., Methods: A total of 252 individuals were included in the clinical trial in accordance with the selection criteria only after clinical study was registered with the Clinical Trial Registry of India (CTRI/2020/09/027796). Scores on the visual analog scale (VAS) and electric pulp test (EPT) on a 1-10 scale were recorded prior to the commencement of therapy. In this double-blinded study, patients were randomly divided by a co-investigator using computer randomisation (www.randomizer.org) into three groups, group A: inferior alveolar nerve blocks (IANB) with 2% lignocaine preheated at 42 °C (injected at 37 °C) ( N  = 84), group B: IANB of 2% lignocaine buffered with 0.18 ml of 8.4% sodium bicarbonate ( N  = 80) and group C: 2% lignocaine ( N  = 88). Excluding the dropouts of individuals ( n  = 11), wherein the anaesthesia failed, a total of 241 people were finally assessed 15 minutes after profound anaesthesia, endodontic access, and intraoperative pain were quantified using VAS. Pain on injection for all three groups was recorded immediately after IANB with VAS. The analysis was performed using one way ANOVA with Tukey's post hoc test and Paired T-Test using SPSS version 21., Results: Preheated, Buffered, and conventional 2% lignocaine showed statistically significant reduction in intraoperative pain ( P  < 0.001) compared to pre-operative but on inter-group comparison preheated and buffered showed highly significant pain reduction compared with conventional 2% lignocaine ( P  < 0.001)., Conclusions: Warm and buffered local anaesthetic (LA) were effective in reducing intraoperative discomfort than conventional LA. Preheated local anesthetics caused the least pain, followed by buffered local anesthetics, while conventional local anesthetics caused the most pain., Competing Interests: Ajinkya M. Pawar is an Academic Editor for PeerJ., (©2022 Gandhi et al.)

The negative externalities of freight transport have caught the attention of scholars and practitioners to study sustainable freight transportation. Past studies have reviewed sustainable logistics from varying perspectives, but the rail mode-specific sustainable logistics has not been thoroughly reviewed. This sets the motivation to review existing research on sustainable rail freight transportation (SRFT). A science mapping approach was used to develop and visualize bibliographic networks of 378 articles published between 2001 and 2022 and indexed in the Scopus database. Four scientometric analysis techniques, namely journal co-citations; countries/organizations/authors co-authorship; document co-citations; and keywords co-occurrence, were employed in the VOSviewer software to reveal conceptual structure, social structure, and influential themes of the SRFT domain. Based on the results, the SRFT knowledge was categorized into six thematic branches (31 sub-branches), namely intermodal transportation for decarbonization; green policies, risk, and energy assessment research; savings in externalities for a sustainable future; decision-making with environmental and economic considerations; case studies and applications in SRFT research; and technological advancements towards sustainability. Finally, future research directions were proposed in the form of research questions. This systematic literature review will facilitate the researchers, practitioners, and policymakers to understand the status quo, existing research gaps, and emerging research topics in the SRFT research domain. This study is restricted to research articles and review articles published in English and indexed in the Scopus database., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background The Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification and management system (O-RADS US) was designed to improve risk assessment and management of ovarian and adnexal lesions. Validation studies including both surgical and nonsurgical treatment as the reference standard remain lacking. Purpose To externally validate O-RADS US in women who underwent either surgical or nonsurgical treatment and to determine if incorporating acoustic shadowing as a benign finding improves diagnostic performance. Materials and Methods This retrospective study included consecutive women who underwent pelvic US between August 2015 and April 2017 at a tertiary referral oncology center. Two independent readers blinded to clinical and histologic outcome assigned an O-RADS risk category and an International Ovarian Tumor Analysis (IOTA) Assessment of Different NEoplasias in the adneXa (ADNEX) model risk of malignancy score to assessable lesions. Reference standards were surgical histopathology or 2-year imaging follow-up. Receiver operating characteristic (ROC) curve analysis was used to evaluate performance of the O-RADS US, ADNEX, and modified O-RADS models incorporating acoustic shadowing. Results In total, 227 women (mean age, 52 years ± 16 [SD]) with 262 ovarian or adnexal lesions were evaluated. Of these lesions, 187 (71%) were benign and 75 (29%) were malignant. The proportion of malignancy was 0% (0 of 100) for O-RADS 2, 3% (one of 32) for O-RADS 3, 35% (22 of 63) for O-RADS 4, and 78% (52 of 67) for O-RADS 5. The area under the ROC curve (AUC) for O-RADS and ADNEX was 0.91 (95% CI: 0.88, 0.94) and 0.95 (95% CI: 0.92, 0.97; P = .01), respectively. The addition of acoustic shadowing as a benign finding improved O-RADS AUC to 0.94 (95% CI: 0.91, 0.96; P = .01). Use of O-RADS 4 as a threshold yielded a sensitivity of 99% (74 of 75; 95% CI: 96, 100) and a specificity of 70% (131 of 187; 95% CI: 64, 77). Conclusion In a tertiary referral oncology center, the Ovarian-Adnexal Reporting and Data System US risk stratification and management system enabled accurate distinction of benign from malignant ovarian and adnexal lesions. Adding acoustic shadowing as a benign finding improved its diagnostic performance. © RSNA, 2022 See also the editorial by Levine in this issue.

Purpose: The purpose of this study was to report a case of microsporidial endotheliitis masquerading as graft rejection after deep anterior lamellar keratoplasty (DALK)., Methods: A 36-year-old man visited the clinic with complaints of blurred vision, redness, pain, watering, and whitish appearance of the black portion of his left eye. On evaluation, there was diffuse stromal edema with epithelial defect and hypopyon. Microbial keratitis resolved with macular grade scar. He underwent DALK. After 3 years, he presented with complaints of sudden diminution of vision in the same eye for 10 days. His unaided visual acuity was counting finger 1 meter. The clinical findings were circumcorneal congestion, diffuse graft edema, Descemet membrane folds, and diffuse keratic precipitates. A presumptive diagnosis of left eye graft rejection was made. Topical steroids were administered. There was significant improvement within a week. However, at 1 month, there was an increase in graft edema after the steroids were tapered. At this point, a diagnosis of endotheliitis of viral origin was made. He was then administered oral antivirals and steroids. There were 2 such waxing and waning episodes of graft edema before the graft failed. Patient underwent penetrating keratoplasty with cataract extraction with intraocular lens implantation., Results: The previous donor and host Descemet endothelium complex was sent for histopathology and polymerase chain reaction. Both histology and polymerase chain reaction were positive for microsporidia., Conclusions: Microsporidial endotheliitis may present as graft rejection. There should be a suspicion of microsporidial infection in cases of features mimicking as endothelial rejection after DALK., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

It is not often that a group of health executives, educators, and professionals gather with the goal of identifying a preferred future for their profession and the patients they serve. It is even more rare when such an assembly results in a clear and actionable plan to follow to achieve that desired future. Nevertheless, the Bridging Pharmacy Education and Practice (BPEP) Summit, an unprecedented collaborative event in June 2022 that involved six sites across the country and more than 300 participants, was just such a convening. In this Commentary we provide a brief overview of this extraordinary summit and the events that led up to it., (© 2022 American Association of Colleges of Pharmacy.)