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Accurate transcription is required for the faithful expression of genetic information. However, little is known about the fidelity of RNA synthesis or the biological consequences of transcription errors in living cells. Here, we review recent developments in massively parallel sequencing technology that allow the fidelity of transcription to be measured with unprecedented accuracy and summarize new observations that provide insight into the role of transcription errors in aging and disease. Taken together, these developments have the potential to change our understanding of mutagenesis itself, and significantly enhance our understanding of the origins of human disease.

Abstract Outputs from new state‐of‐the‐art climate models under the Coupled Model Inter‐comparison Project phase 6 (CMIP6) promise improvement and enhancement of climate change projections information for Australia. Here we focus on three key aspects of CMIP6: what is new in these models, how the available CMIP6 models evaluate compared to CMIP5, and their projections of the future Australian climate compared to CMIP5 focussing on the highest emissions scenario. The CMIP6 ensemble has several new features of relevance to policymakers and others, for example, the integrated matrix of socioeconomic and concentration pathways. The CMIP6 models show incremental improvements in the simulation of the climate in the Australian region, including a reduced equatorial Pacific cold tongue bias, slightly improved rainfall teleconnections with large‐scale climate drivers, improved representation of atmosphere and ocean extreme heat events, as well as dynamic sea level. However, important regional biases remain, evident in the excessive rainfall over the Maritime Continent and rainfall pattern biases in the nearby tropical convergence zones. Projections of Australian temperature and rainfall from the available CMIP6 ensemble broadly agree with those from CMIP5, except for a group of CMIP6 models with higher climate sensitivity and greater warming and increase in some extremes after 2050. CMIP6 rainfall projections are similar to CMIP5, but the ensemble examined has a narrower range of rainfall change in austral summer in Northern Australia and austral winter in Southern Australia. Overall, future national projections are likely to be similar to previous versions but perhaps with some areas of improved confidence and clarity.

Abstract Background Cancer stage at diagnosis is an important prognostic indicator for patient outcomes, with detection at later stages associated with increased mortality and morbidity. The impact of cancer stage on patient-reported outcomes is poorly understood. This research aimed to understand symptom burden and health related quality of life (HRQoL) impact by cancer stage for ten cancer types: 1) ovarian, 2) lung, 3) pancreatic, 4) esophageal, 5) stomach, 6) head and neck, 7) colorectal, 8) anal, 9) cervical, and 10) liver and bile duct. Methods Ten narrative literature reviews were performed to identify and collate published literature on patient burden at different stages of disease progression. Literature searches were conducted using an AI-assisted platform to identify relevant articles published in the last five (2017–2022) or ten years (2012–2022) where articles were limited. Conference abstracts were searched for the last two years (2020–2022). The geographic scope was limited to the United States, Canada, Europe, and global studies, and only journal articles written in English were included. Results A total of 26 studies with results stratified by cancer stage at diagnosis (and before treatment) were selected for the cancer types of lung, pancreatic, esophageal, stomach, head and neck, colorectal, anal, and cervical cancers. Two cancer types, ovarian cancer, and liver and bile duct cancer did not return any search results with outcomes stratified by disease stage. A general trend was observed for worse patient-reported outcomes in patients with cancer diagnosed at an advanced stage of disease compared with diagnosis at an earlier stage. Advanced disease stage was associated with greater symptom impact including general physical impairments such as pain, fatigue, and interference with functioning, as well as disease/region-specific symptom burden. Poorer HRQoL was also associated with advanced disease with commonly reported symptoms including anxiety and depression. Conclusions Overall, the general trend for greater symptom burden and poorer HRQoL seen in late stage versus early-stage disease across the included cancer types supports the importance for early diagnosis and treatment to improve patient survival and decrease negative impacts on disease burden and HRQoL.

Abstract Background The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions. Methods Twenty horses were randomly assigned to 1 of 2 groups (n = 10): control (placebo paste) or NSAID (phenylbutazone 4.4 mg/kg orally once daily for 9 days). Fecal samples were collected on days 0 and 10 and analyzed with respect to microbiota (16S rDNA gene sequencing), metabolomic (untargeted metabolites), and host exfoliated cell transcriptomic (exfoliome) changes. Data were analyzed and integrated using a variety of computational techniques, and underlying regulatory mechanisms were inferred from features that were commonly identified by all computational approaches. Results Phenylbutazone induced alterations in the microbiota, metabolome, and host transcriptome. Data integration identified correlation of specific bacterial genera with expression of several genes and metabolites that were linked to oxidative stress. Concomitant microbiota and metabolite changes resulted in the initiation of endoplasmic reticulum stress and unfolded protein response within the intestinal mucosa. Conclusions Results of integrative analysis identified an important role for oxidative stress, and subsequent cell signaling responses, in a large animal model of GI inflammation. The computational approaches for combining non-invasive platforms for unbiased assessment of host GI responses (e.g., exfoliomics) with metabolomic and microbiota changes have broad application for the field of gastroenterology. Video Abstract

Purpose: This study aimed to evaluate the safety and effectiveness of mini-open carpal tunnel release (mOCTR) using best-evidence synthesis methods. Methods: We systematically searched for prospective studies published from January 2013 to July 2023 that reported outcomes from a minimum of 50 mOCTR cases. The outcomes included Quick Disabilities of the Arm, Shoulder, and Hand Questionnaire, Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), pain visual analog scale (VAS), complication rate, and reoperation rate. Data analysis was performed using a random-effects meta-analysis, with metaregression to identify the associations between patient- and study-level factors with surgical outcomes. Results: The meta-analysis included 23 studies with 2,303 patients followed for median durations ranging from 6 to 12 months depending on the outcome. Mini-open carpal tunnel release resulted in statistically significant and clinically important improvements in Quick Disabilities of the Arm, Shoulder, and Hand Questionnaire (mean difference = −25.5; 95% confidence interval [CI]: −36.4 to −14.5; P < .001), BCTQ-SSS (mean difference = −2.2; 95% CI: −2.5 to −1.9; P < .001), BCTQ-FSS (mean difference = −2.1; 95% CI: −2.4 to −1.7; P < .001), and pain VAS (mean difference = −5.1; 95% CI: −6.2 to −4.1; P < .001). The sole predictor of improvement in BCTQ-SSS, BCTQ-FSS, and pain VAS was a higher preoperative score for the respective variable (all P < .001). The risk of complications (mainly short-term pillar pain or scar complications) was 8.9% (95% CI: 4.0%–13.8%) and increased with longer incision lengths (P = .008). Revision carpal tunnel release was performed in 0.6% (95% CI: 0.1%–1.0%) of the cases during follow-up. No cases of median nerve transection were reported. Conclusions: Based on a best-evidence meta-analysis of contemporary studies, mOCTR significantly improved function and pain, with a relatively low risk of mainly temporary complications. Patient outcomes after mOCTR were influenced by patient symptomatology and surgical incision length. Clinical relevance: Mini-open carpal tunnel release is an effective surgical option that significantly improves symptoms and function, especially for patients with more severe baseline dysfunction. Surgeons should use the shortest incision that allows adequate visualization to safely divide the transverse carpal ligament.

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Previous reports have described failures of modular fluted tapered femoral stems secondary to fatigue failure at the modular junction. However, the present study is the first reported case of modular fluted tapered femoral component failure involving atraumatic fracture of the proximal body following revision total hip arthroplasty. The failure occurred in a 52-year-old female with a history of postmenopausal osteoporosis on bisphosphonates who sustained an atraumatic fracture of the proximal body of a modular revision femoral stem. In the present case, revision THA utilizing a wider proximal body segment with proximal augmentation using strut allografts for biological and mechanical support provided the patient with a stable construct at 30-month follow-up.

Background: Trabecular metal augments (TMAs) have been extensively used in revision total hip arthroplasty (THA) to address acetabular bone defects. However, limited data exists regarding TMA utilization during primary THA. This study aims to assess the clinical and radiographic outcomes of TMAs used during primary THA. Methods: A single-institution retrospective case series of primary THA patients treated with TMA between 2010 and 2019 was performed. Patient demographics, complications, and revisions were recorded. Cup position, center of rotation, leg length, and radiolucent lines were assessed radiographically. The Kaplan-Meier method was used to compute implant survivorship. Results: Twenty-six patients (30 hips) were included with average age of 52.6 ± 15.3 years (range: 22-78) and mean follow-up of 4.1 ± 2.1 years (range: 2.0-8.9). Most TMAs were indicated for developmental dysplasia of the hip (n = 18; 60.0%). On average, hip center of rotation was lowered 1.5 ± 1.3 cm and lateralized 1.2 ± 1.5 cm, while leg length and global offset were increased by 2.4 ± 1.2 cm and 0.4 ± 1.0 cm, respectively. At final follow-up, 3 hips (10.0%) required revision: one (3.3%) for aseptic loosening and 2 (6.7%) for instability. No patients had progressive radiolucent lines at final follow-up. Five-year survival with aseptic loosening and all-cause revision as endpoints was 100% (95% confidence interval: 90.0%-100.0%) and 92.1% (95% confidence interval: 81.3%-100.0%), respectively. One patient required revision for aseptic loosening after the 5-year mark. Conclusions: Trabecular metal augmentation during primary THA demonstrates satisfactory early to mid-term outcomes. TMA is a viable option for complex primary THA when bone loss is encountered or secondary support is required. Level of Evidence: Level IV.

Background:. Delay in surgical treatment for carpal tunnel syndrome (CTS) may result in long-term decreased functional outcomes. Few investigators have examined the relationship between type of health insurance plan and time to definitive treatment of CTS following diagnosis. We investigated the relationship between insurance type, treatment decision, and the time between diagnosis and surgery across groups. Methods:. This was a retrospective cohort study using the MarketScan Commercial Claims and Encounters Database 2011–2020. We used χ2 tests, linear regression, and logistic regression models to analyze demographic data and the time lag interval between CTS diagnosis and treatment. Results:. Overall, 28% of high-deductible health plan (HDHP) patients underwent carpal tunnel release, compared with 20% of traditional insurance patients (P < 0.001). HDHPs are defined by the internal revenue service as a deductible of $1400 for an individual or $2800 for a family per year. The odds of undergoing surgery versus no treatment for HDHP patients were 47% higher than traditional patients (P < 0.001). Among the patients who underwent surgery, HDHP patients underwent surgery 65 days earlier on average following diagnosis compared with traditional patients (P < 0.001). Conclusions:. Patients with HDHPs who receive a diagnosis of CTS are more likely to undergo surgery, with a shorter time lag between diagnosis and surgery. The results from this study call attention to differences in surgical decision-making between patients enrolled in different insurance plans.

Graduate students consider research as the most challenging task in their studies. Aside from the researches that they do in their course work, they are also required to conduct, write, and defend their thesis or dissertation which is the terminal output of the graduate program. In spite of the challenges in research work, there are graduate students who did researches that were published in local and international journals. Though publication is not yet a requirement, they decided to do research and had them published. However, the Commission on Higher Education issued CMO 15 s. 2019 “Policies, Standards and Guidelines for Graduate Programs” requiring publication of a research work in an internationally or nationally refereed and indexed journal or have a juried creative work outlet before a graduate student earns the degree. In consideration of this policy, the study looked into the motivations, experiences and needs of selected graduate students who have engaged in research and publication. The findings revealed that their motivations are professors’ encouragement, course requirements, new learning experience, collaboration, and promotion. In describing their experiences, they found it enriching, collaborative, fulfilling, and challenging. Their needs are mentoring, research capability building, having a research community, financial support and incentives, and providing relevant information. From the findings, it can be concluded that graduate students will be able to do research with the right motivation and support from the faculty. Research and publication are fulfilling and enriching but challenging. The experiences and needs of the selected graduate students can be used as inputs in the development of a research and publication program for graduate students.

Extra-articular deposition of monosodium urate crystals is a widely recognized manifestation of gout. However, gouty infiltration of flexor tendons in the hand resulting in tendon rupture is exceedingly rare. This case report highlights a patient with gouty infiltration of flexor tendons in the right middle finger resulting in rupture of both the flexor digitorum profundus and flexor digitorum superficialis. Given the extent of gouty infiltration and need for pulley reconstruction, the patient was treated with two-stage flexor tendon reconstruction. Febuxostat was prescribed preoperatively to limit further deposition of monosodium urate crystals and continued postoperatively to maximize the potential for long-lasting results. Prednisone was prescribed between the first- and second-stage operations to prevent a gout flare while the silicone rod was in place. In summary, tendon rupture secondary to gouty infiltration is the most likely diagnosis in patients with a history of gout presenting with tendon insufficiency.

Abstract Background Thumb carpometacarpal (CMC) joint arthritis is one of the most prevalent arthritic conditions commonly treated with trapeziectomy alone or trapeziectomy with ligament reconstruction and tendon interposition (LRTI). We evaluate the cost-effectiveness and value of perfect and sample information of trapeziectomy alone, LRTI, and non-operative treatment. Methods A societal perspective decision tree was modeled. To understand the value of future research in comparing quality-of-life after trapeziectomy, LRTI, and non-operative management we characterized uncertainty by fitting distributions to EQ-5D utility data published from the United Kingdom hand surgery registry. We used Monte Carlo simulation for the probabilistic sensitivity analysis and to evaluate the value of perfect and sample information. Results Both trapeziectomy alone and LRTI were cost-effective compared to non-operative management ($2,540 and $3,511/QALY respectively). Trapeziectomy alone (base case total cost $8,251, QALY 14.08) was dominant compared to LRTI (base case total cost $8,798, QALY 13.34). However, probabilistic sensitivity analysis suggested there is a 12.5% chance LRTI may be preferred at a willingness-to-pay of $50,000/QALY. Sensitivity analysis revealed postoperative utilities are the most influential factors in determining cost-effectiveness. The value of perfect information was approximately $1,503/person. A study evaluating the quality-of-life of 1,000 patients in each arm undergoing trapeziectomy alone or LRTI could provide an expected $1,117 of information value. With approximately 40,000 CMC arthroplasties performed each year in the U.S., the annual value is close to $45 million. Conclusions Trapeziectomy without LRTI appears to be the most cost-effective procedure in treating late-stage CMC arthritis and should be considered as first-line surgical treatment. There is substantial societal value in conducting additional research to better understand the relative quality-of-life improvements gained from these two common hand surgeries.

Summary: In low- and middle-income countries (LMICs), the fields of medicine and public health grapple with numerous challenges that continue to hinder patients' access to healthcare services. ChatGPT, a publicly accessible chatbot, has emerged as a potential tool in aiding public health efforts in LMICs. This viewpoint details the potential benefits of employing ChatGPT in LMICs to improve medicine and public health encompassing a broad spectrum of domains ranging from health literacy, screening, triaging, remote healthcare support, mental health support, multilingual capabilities, healthcare communication and documentation, medical training and education, and support for healthcare professionals. Additionally, we also share potential concerns and limitations associated with the use of ChatGPT and provide a balanced discussion on the opportunities and challenges of using ChatGPT in LMICs.

Katydids produce sound for signaling and communication by stridulation of the tegmina. Unlike crickets, most katydids are known to sing at ultrasonic frequencies. This has drawn interest in the investigation of the biophysics of ultrasonic sound production, detection, evolution, and ecology (including predator–prey interactions) of these katydids. However, most of these studies are based on species from the Neotropics, while little is known about katydid species from the hyperdiverse region of Southeast Asia. To address this, a concerted effort to document, record, and describe the calling songs of Southeast Asian katydids, especially species that call at ultrasonic frequencies, was made. A study spanning two years (2018–2020) in the Malay Peninsula (Singapore and Malaysia), Borneo (Brunei Darussalam and Sabah), and the Philippines revealed previously unknown calls of 24 katydid species from four subfamilies. The calling songs of Southeast Asian katydid species are highly diversified in terms of time and frequency. Call structure can range from isolated syllables (e.g., Holochlora), continuous trills (e.g., Axylus philippinus), to short pulse-trains (e.g., Euanisous teuthroides) and complex echemes (e.g., Conocephalus spp.), with 87.5% of species having ultrasonic peak frequencies and 12.5% being considered extreme ultrasonic callers (peak frequency >40 kHz). The call spectrum ranges from tonal (e.g., spectral entropy is 6.8 in Casigneta sp. 2) to resonant (entropy is 8.8 in Conocephalus cognatus). Of the 24 species whose calls are described here, we imaged and described the sound-producing structures of 18. This study provides a preliminary overview of the acoustic diversity of katydids in Southeast Asia, and the authors hope to inspire further investigation into the bioacoustics of little-known katydids from these areas. Amassing a database of calling songs and sound-producing organ illustrations from different species is important to address taxonomic impediments while advancing our knowledge about the bioacoustics of Southeast Asian katydids.

Abstract Background Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. Methods This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. Results In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3–84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16–2.13) and 2.14 (95% CI: 1.65–2.77), respectively. Conclusion A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

The essence of treating scar contractures lies in covering the skin deficit after releasing the contractures, typically using flaps or skin grafts. However, the specific characteristics of scar contractures, such as their location, shape, and size, vary among patients, which makes surgical planning challenging. To achieve excellent outcomes in the treatment of scar contractures, we have developed a dimensional classification system for these contractures. This system categorizes them into four types: type 1 (superficial linear), type 2-d (deep linear), type 2-s (planar scar contractures confined to the superficial layer), and type 3 (planar scar contractures that reach the deep layer, i.e., three-dimensional scar contractures). Additionally, three factors should be considered when determining surgical approaches: the size of the defect, the availability of healthy skin around the defect, and the blood circulation in the defect bed. Type 1 and type 2-d are linear scars; thus, the scar is excised and sutured in a straight line, and the contracture is released using z-plasty or its modified methods. For type 2-s, after releasing the scar contracture band, local flaps are indicated for small defects, pedicled perforator flaps for medium defects, and free flaps and distant flaps for large defects. Type 2-s has good blood circulation in the defect bed, so full-thickness skin grafting is also a suitable option regardless of the defect’s size. In type 3, releasing the deep scar contracture will expose important structures with poor blood circulation, such as tendons, joints, and bones. Thus, a surgical plan using flaps, rather than skin grafts, is recommended. A severity classification and treatment strategy for scar contractures have not yet been established. By objectively classifying and quantifying scar contractures, we believe that better treatment outcomes can be achieved.

Vertical transmission of Trypanosoma cruzi (T. cruzi) become a globalized health problem accounting for 22% of new cases of Chagas disease (CD). Congenital infection is now considered the main route of CD spread in non-endemic countries where no routine disease testing of pregnant women is implemented. The main mechanisms that lead to fetal infection by T. cruzi remain poorly understood. Mother-to-child transmission may occur when bloodstream trypomastigotes interact with the syncytiotrophoblasts (SYNs) that cover the placenta chorionic villi. These highly specialized cells function as a physical barrier and modulate immune responses against pathogen infections. To model the human placenta environment, we have previously used a three-dimensional (3D) cell culture system of SYNs that exhibits differentiation characteristics comparable to placental trophoblasts. Further, we have shown that 3D-grown SYNs are highly resistant to T. cruzi infection. In this work, we used RNA sequencing and whole transcriptome analysis to explore the immunological signatures that drive SYNs’ infection control. We found that the largest category of differentially expressed genes (DEGs) are associated with inflammation and innate immunity functions. Quantitative RT-PCR evaluation of selected DEGs, together with detection of cytokines and chemokines in SYNs culture supernatants, confirmed the transcriptome data. Several genes implicated in the Toll-like receptors signaling pathways were upregulated in 3D-grown SYNs. In fact, TLR2 blockade and TLR3/7 knockdown stimulated T. cruzi growth, suggesting that these molecules play a significant role in the host cell response to infection. Ingenuity Pathway Analysis of DEGs predicted the activation of canonical pathways such as S100 protein family, pathogen induced cytokine storm, wound healing, HIF1α signaling and phagosome formation after T. cruzi exposure. Our findings indicate that SYNs resist infection by eliciting a constitutive pro-inflammatory response and modulating multiple defense mechanisms that interfere with the parasite’s intracellular life cycle, contributing to parasite killing and infection control.

Abstract Background Cancer represents a significant source of disease burden in the United States (US), both clinically and economically. Diagnosis and treatment of cancer at earlier stages may reduce this burden. To better understand potential impacts of earlier diagnosis, healthcare costs among patients with cancer were assessed by cancer type and stage at diagnosis. Methods A retrospective analysis was conducted using Optum’s de-identified Integrated Claims-Clinical data set with Enriched Oncology, which includes data from Medicare Advantage and commercially insured members. Adult members newly diagnosed with solid tumor cancers, cancer stage at diagnosis (diagnosed 1/1/2016–6/30/2020), and continuous enrollment for at least one month post diagnosis were identified. Patients with breast, cervical, colorectal, lung, ovarian, or prostate cancer were reported. Mean standardized costs (2020 USD) were calculated in each month on an annual and cumulative basis through four years post-cancer diagnosis. In each month, costs were calculated for those with continuous enrollment and no death reported in the month. Mean annual cost per patient was estimated by summing month one to 12 mean costs and stratifying by stage at cancer diagnosis; annual year one to four costs were summed to determine cumulative costs. Results Among members diagnosed 2016–2020 with breast, cervical, colorectal, lung, ovarian, or prostate cancer, 20,422 eligible members were identified. Mean costs increased by stage of diagnosis across all cancers at the annual and cumulative level through year four post diagnosis. Cumulative mean costs grew over time at a relatively similar rate across stages I to III and more dramatically in stage IV, except for cervical and lung cancer where the rate was relatively stable or slightly fluctuated across stages and ovarian cancer where stages III and IV both increased more sharply compared to stages I and II. Conclusions Mean annual and cumulative healthcare costs through year four post cancer diagnosis were significantly higher among those diagnosed at later versus earlier cancer stages. The steeper increase in cumulative costs among those diagnosed in stage IV for many cancer types highlights the importance of earlier cancer diagnosis. Earlier cancer diagnosis may enable more efficient treatment, improve patient outcomes and reduce healthcare costs.

Background:. We aimed to review common patient concerns after surgical repair of distal radius fracture (DRF) to identify potential interventions to improve the gap between expectation and education for DRF patients. Methods:. We conducted a retrospective cohort study of 100 consecutive patients who underwent surgical repair of DRF at a level I trauma center. Patient-initiated communication notes were reviewed with thematic analysis to identify the common reasons patients required additional information. We used the Patient Education Materials Assessment Tool to score the available educational resources for DRF patients for the understandability and actionability of the educational materials provided to the patients. Results:. Of 165 patient communication episodes, 88.5% occurred postoperatively. The most common concerns were pain (30, 15.4%) and surgical site changes (24, 12.3%). Most communications (171, 83.4%) were resolved with patient education through instruction or reassurance. The reviewed materials did not address pain or surgical site changes. No reviewed materials provided actionable steps patients could take to facilitate recovery. Conclusions:. Pain management and normal wound healing were the most common surgical concerns of DRF patients. We identify opportunities to improve expectation-setting in online materials and during face-to-face education to create a more patient-centered perioperative experience.

Background: This study aims to examine differences in postoperative complications and opioid consumption associated with perioperative peripheral nerve block (PNB) utilization during primary total knee arthroplasty (TKA). Methods: The Premier Healthcare Database was queried for adult patients who underwent primary, elective TKA from 2015 to 2020. Patients who received a femoral or adductor canal PNB were compared to patients who did not. PNB utilization was trended from 2015 to 2020. Univariate and multivariate regression analyses were performed to assess differences in the 90-day risk of postoperative complications between groups. The average inpatient opioid consumption in morphine milligram equivalents was assessed as a function of length of stay. Results: Overall, 609,991 patients were included. PNB utilization increased from 9.29% in 2015 to 30.3% in 2020. After controlling for confounders, the PNB cohort was more likely to have same-day discharge (adjusted odds ratio [aOR] 1.88) and had a decreased risk of periprosthetic joint infection (aOR 0.87), pulmonary embolism (aOR 0.81), and respiratory failure (aOR 0.78). However, there was an increased risk of seroma (aOR 1.75) and hematoma (aOR 1.22) associated with PNB utilization. Lower average overall opioid exposure was seen in the PNB cohort vs no-PNB cohort (82.1 ± 194.7 vs 89.4 ± 214.1 morphine milligram equivalents, P < .001). Conclusions: PNB utilization during primary TKA is associated with a shorter length of stay and decreased risk of multiple postoperative complications, as well as reduced postoperative opioid consumption. These data provide evidence in support of the safety and efficacy of this emerging practice. However, the clinical relevance of an increased risk of seroma and hematoma formation may warrant further investigation.

Taiwan features steep terrain and a fragile geological environment accompanied by frequent earthquakes and typhoons annually. Meanwhile, with the booming economy and rapid population growth, activities pivot from metropolises to Taiwan's suburban and mountain areas. However, for example, the Neikuihui tribe in northern Taiwan experiences landslide disasters during extreme rainfall events. To rapidly examine landslide risk in the tribe area for preliminary disaster management, the well-known principle of risk, which comprises hazard, exposure, and vulnerability, was carefully adapted to scrutinize 14 slope units around the Neikuihui tribe region. The framework of risk zoning is improved based on the previous quantified findings regarding the inventory of the deep-seated landslides in southern Taiwan. Moreover, the proposed procedures comprehensively assess susceptibility, activity, exposure, and vulnerability of each slope unit. The rapid risk zoning analysis of multi-slope units delivers a sloping unit with a high level of landslide risk, and this slope unit did suffer from landslide disasters in the 2016 typhoon event. This study preliminarily proves that the proposed framework and details of rapid risk zoning can help identify a relatively high-risk slope unit around a tribal region and address pre-countermeasures for disaster management.

Purpose: Given limited ambulatory access to genetics specialists, innovative service delivery solutions are needed. Electronic consultation (e-consult) programs are growing to connect clinicians to specialists. We explored the utilization and outcomes of a genetics and genomics e-consult program at Massachusetts General Hospital system in its first year. Methods: A retrospective observational analysis of genetics e-consults ordered between April 2021 and March 2022. Results: In its first year, the e-consult service triaged 153 requests and completed 122 in a median of 2.0 days. Of the 97 e-consults with actionable recommendations, there was documentation that most ordering clinicians followed through (82%). A variety of providers used the service, though the majority (77%) were generalists. Conclusion: e-Consult models should be considered as one way to increase access to genetics expertise.

Cardiorespiratory fitness is a key component of health-related fitness. It is a necessary focus of improvement, especially for those that have poor fitness and are classed as untrained. However, much research has shown individuals respond differentially to identical training programs, suggesting the involvement of a genetic component in individual exercise responses. Previous research has focused predominantly on a relatively low number of candidate genes and their overall influence on exercise responsiveness. However, examination of gene-specific alleles may provide a greater level of understanding. Accordingly, this study aimed to investigate the associations between cardiorespiratory fitness and an individual's genotype following a field-based endurance program within a previously untrained population. Participants (age: 29 ± 7 years, height: 175 ± 9 cm, mass: 79 ± 21 kg, body mass index: 26 ± 7 kg/m2) were randomly assigned to either a training (n = 21) or control group (n = 24). The training group completed a periodized running program for 8-weeks (duration: 20-30-minutes per session, intensity: 6-7 Borg Category-Ratio-10 scale rating, frequency: 3 sessions per week). Both groups completed a Cooper 12-minute run test to estimate cardiorespiratory fitness at baseline, mid-study, and post-study. One thousand single nucleotide polymorphisms (SNPs) were assessed via saliva sample collections. Cooper run distance showed a significant improvement (0.23 ± 0.17 km [11.51 ± 9.09%], p < 0.001, ES = 0.48 [95%CI: 0.16-0.32]), following the 8-week program, whilst controls displayed no significant changes (0.03 ± 0.15 km [1.55 ± 6.98%], p = 0.346, ES = 0.08, [95%CI: -0.35-0.95]). A significant portion of the inter-individual variation in Cooper scores could be explained by the number of positive alleles a participant possessed (r = 0.92, R2 = 0.85, p < 0.001). These findings demonstrate the relative influence of key allele variants on an individual's responsiveness to endurance training.

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Background:. The prevalence of bone stimulator use among nonoperatively and operatively managed scaphoid nonunion patients is unknown. We hypothesize that bone stimulators are a relatively underutilized treatment for scaphoid nonunion patients. Methods:. We used the 2009–2017 Truven Marketscan Research Databases to identify patients with closed scaphoid fractures and performed an analysis of variance test to determine resource utilization and bone stimulator use among these patients. Results:. A total of 36,611 patients with scaphoid fractures were identified: 30,143 were managed nonoperatively and 6468 were managed operatively. Nonunion was diagnosed in 500 (1.66%) nonoperatively and in 1211 (19%) operatively managed patients. Bone stimulators were used in less than 2% of nonoperatively and operatively managed scaphoid nonunion patients. Conclusion:. Lack of trust in the technology and heterogenous (and occasionally burdensome) requirements for insurance approval are barriers to bone stimulator use; however, surgeons should examine how this technology may fit into the treatment algorithm for these difficult cases.

Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.

Background:. The increase in virtual conferences during the COVID-19 pandemic provided unexpected advantages such as increased accessibility, while also creating concern about the effectiveness of online networking and career development. Given that a variety of conference attributes are impacted by changes in conference format, we sought to investigate how plastic surgeons prioritize key aspects of conference conduct. Methods:. We sent a survey based on conjoint analysis, a statistical method for evaluating consumer preferences, to active members of the American Society of Plastic Surgeons. Respondents were asked to choose between pairs of conference options, each with unique attributes. Their answers were used to calculate feature importance values and utility coefficients for the conference attributes. Subgroup analyses were conducted based on demographic factors. Results:. A total of 263 respondents completed the survey. Respondents were mostly White (181 individuals [68.8%]) and men (186 [70.7%]). Nearly half (122 [46.4%]) had been practicing 20 or more years. Conference attributes with the highest feature importance values (SDs) were cost of attendance (30.4% [14.2%]) and conference format (28.8% [14.2%]). Equity initiatives (14.5% [10.1%]), reimbursement for cost (11.1% [5.7%]), and opportunities for networking (9.5% [6.0%]) had intermediate feature importance values. Environmental impact had the lowest feature importance (5.7% [3.8%]). Conclusions:. Surgeons’ conference preferences depend highly on format and the presence of equity initiatives, both of which can be incorporated or modified in future conferences to ensure inclusive and successful events. Meanwhile, environmental impact is less important to surgeons, suggesting a pressing need to bring sustainability issues to their attention.

Cementless fixation during total hip arthroplasty (THA) is the predominant mode of fixation utilized for both acetabular and femoral components during elective primary THAs performed in the United States. This study aims to compare early complication and readmission rates between primary THA patients receiving cemented versus cementless femoral fixation. The 2016–2017 National Readmissions Database was queried to identify patients undergoing elective primary THA. Postoperative complication and readmission rates at 30, 90, and 180 days were compared between cemented and cementless cohorts. Univariate analysis was conducted to compare differences between cohorts. Multivariate analysis was performed to account for confounding variables. Of 447,902 patients, 35,226 (7.9%) received cemented femoral fixation, while 412,676 (92.1%) did not. The cemented group was older (70.0 vs. 64.8, p < 0.001), more female (65.0% vs. 54.3%, p < 0.001), and more comorbid (CCI 3.65 vs. 3.22, p < 0.001) compared to the cementless group. On univariate analysis, the cemented cohort had decreased odds of periprosthetic fracture at 30 days postoperatively (OR: 0.556, 95%-CI 0.424–0.729, p < 0.0001), but higher odds of hip dislocation, periprosthetic joint infection, aseptic loosening, wound dehiscence, readmission, medical complications, and death at all timepoints. On multivariate analysis, the cemented fixation cohort demonstrated reduced odds of periprosthetic fracture at all postoperative timepoints: 30 (OR: 0.350, 95%-CI 0.233–0.506, p < 0.0001), 90 (OR: 0.544, 95%-CI 0.400–0.725, p < 0.0001), and 180 days (OR: 0.573, 95%-CI 0.396–0.803, p = 0.002). Cemented femoral fixation was associated with significantly fewer short-term periprosthetic fractures, but more unplanned readmissions, deaths, and postoperative complications compared to cementless femoral fixation in patients undergoing elective THA.

Background:. Plastic and Reconstructive Surgery (PRS) recently developed an open access counterpart, PRS Global Open (PRS-GO), to increase dissemination of research in an efficient and widespread manner. We aimed to (1) examine the differences in the dissemination of research published in PRS and PRS-GO, and (2) identify differences in the authorship between the journals. Methods:. We extracted data on Altmetric Attention Scores, article mentions, citations, and author characteristics using the Altmetric Explorer Database from January 1, 2018, to January 1, 2020. We stratified research outputs into traditional dissemination and social media dissemination. Additionally, multivariable linear regression models were used to examine differences in dissemination between the journals. Results:. A total of 1798 articles were included in the analysis (PRS = 1031, PRS-GO = 767). The average Altmetric Attention Score was higher for PRS compared with PRS-GO (PRS = 15.2, PRS-GO = 8.1). Articles in PRS had a greater Altmetric Attention Score (β-coefficient: 7.50, P < 0.001), higher measures of traditional dissemination (β-coefficient: 3.11, P < 0.001), and higher measures of social media dissemination than articles in PRS-GO (β-coefficient: 4.38, P = 0.73). Conclusions:. Despite being an open access journal, PRS-GO had significantly fewer measures of social media and traditional dissemination compared with PRS. Given that numerous factors may influence the dissemination of scientific literature, it is imperative that publications identify specific ways to provide a fair advantage for both researchers and readers. Additional initiatives to engage readership for open access may include creative campaigns targeting an appropriate audience.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

In this article results of the multicenter trial are displayed. Data of successful efficacy of trastuzumab treatment in HER2 positive gastric cancer patients has shown.

Extreme warming events can profoundly alter the transmission dynamics of mosquito-borne diseases by affecting mosquito life-history traits (e.g. survival, growth and reproduction). At local scales, temperatures are determined largely by vegetation structure and can be dramatically altered by drivers of land-use change (e.g. forest conversion). Disturbance activities can also hinder the buffering capacity of natural habitats, making them more susceptible to seasonal climate variation and extreme weather events (e.g. droughts). In experiments spanning three years, we investigated the interactive effects of tropical forest conversion and climate on fine-scale temperature, and the consequences for mosquito larval development. This study was conducted in the northern Malaysian Bornean state of Sabah using local Aedes albopictus mosquitoes; important vectors of dengue, chikungunya and Zika viruses. We demonstrate that variation in temperatures due to forest conversion dramatically increases development rates in Ae . albopictus mosquitoes. However, this effect was mediated by an El Niño Southern Oscillation (ENSO) drought event. In normal years, mean temperatures did not differ between land-use types, however mosquitoes reared in oil palm plantations typically emerged 2–3 days faster than in logged forests. During an ENSO drought, mean temperatures did differ between land-use types, but surprisingly this did not result in different mosquito development rates. Driving this idiosyncratic response may be the differences in daily temperature fluctuations between the land-use types that either push mosquito larvae towards optimal development, or over the thermal optimum, thereby reducing fitness. This work highlights the importance of considering the synergistic effects of land-use and seasonal climate variations for predicting the thermal response of a key mosquito life-history trait driving disease transmission dynamics.

Background: TERT encodes the telomerase reverse transcriptase, which is responsible for maintaining telomere ends by addition of (TTAGGG) n nucleotide repeats at the telomere. Recent genome-wide association studies have found common genetic variants at the TERT-CLPTM1L locus (5p15.33) associated with an increased risk of several cancers. Results: Data were acquired for 1627 variants in 1092 unrelated individuals from 14 populations within the 1000 Genomes Project. We assessed the population genetics of the 5p15.33 region, including recombination hotspots, diversity, heterozygosity, differentiation among populations, and potential functional impacts. There were significantly lower polymorphism rates, divergence, and heterozygosity for the coding variants, particularly for non-synonymous sites, compared with non-coding and silent changes. Many of the cancer-associated SNPs had differing genotype frequencies among ancestral groups and were associated with potential regulatory changes. Conclusions: Surrogate SNPs in linkage disequilibrium with the majority of cancer-associated SNPs were functional variants with a likely role in regulation of TERT and/or CLPTM1L. Our findings highlight several SNPs that future studies should prioritize for evaluation of functional consequences.

Статья посвящена анализу стратегий копинг­поведения, исполь­ зуемых людьми в ситуации развода. В настоящее время механизмы психологической защиты и механизмов совладания (копинг­поведе­ ние) рассматриваются как важнейшие формы адаптационных про­ цессов и реагирования индивидов на стрессовые ситуации. По мне­ нию множества исследователей, выбор человеком конструктивных стратегий копинг­поведения в ситуации развода помогает адаптиро­ ваться к этой сложной жизненной ситуации, а также предотвратить развитие посттравматического стресса как реакции на это травми­ рующее событие. Рассматривается взаимосвязь пережитого травма­ тического опыта с приспособлением к текущей травме развода. На основе проведенного исследования делается вывод о том, что в си­ туации развода наиболее конструктивным вариантом копинг­страте­ гий является проблемно­ориентированный копинг. Мақала адамдардың неке бұзу жағдайында қолданатын копинг­ тік жүріс­тұрыс стратегияларын талдауға арналған. Қазіргі уақытта психологиялық қорғаныс механизмдері мен копингтік жүріс­тұрыс механизмдері индивидтердің қиын стрестік жағдайларда бейімделу процестері мен жауап берудің маңызды формалары болып табылады. Мақала авторларының пікірінше адамның неке бұзу жағдайында ко­ пингтік жүріс­тұрыстың конструктивтік стратегияларын таңдау осы қиын өмірлік жағдайға бейімделуге көмектесіп, осы жарақаттық оқи­ ға жауап ретінде пайда болатын жарақаттан кейінгі стрестің пайда болмауына себеп болады. Өткен жарақаттық тәжірибемен ажырасу жағдайына бейімделудің арасындағы өзара байланыс қарастырылған. Жүргізілген зерттеу негізінде ажырасу жағдайында мәселені шешуге бағытталған копинг түрі тиімдірек болатындығы анықталған.

As part of an ethnographic study, the impact of foreign postings on spouses who accompany military personnel was explored. Individual interviews and focus groups with 34 British military spouses based in one location in southern Europe were conducted. Key findings suggested that reaction to a foreign posting was a reflection of personal attitudes, prior experiences, support, ability to adjust to change and strength of relationship with the serving spouse and community. For many the experience was positive due to the increased opportunity for family time, for others this helped to compensate for the difficulties experienced. Some military spouses experienced significant distress on the posting, particularly if the family was not well-supported. The potential implications of military spouses not adapting to foreign postings have significant implications for healthcare practice. Provision of more appropriate support resources before and during the posting would facilitate the transition for the military spouse and their family.

This study aimed to examine trans fatty acids (TFA) content of 142 individual food items, including bakery, fast food, and other fatty food that may contain high level of TFA. TFA was detected in all samples, except for four samples including one plain bread, one sponge cake, and two batter-made foods (egg roll and eggette) samples. For those found to contain detectable TFA, the content ranged up to 4.7 g/100 g of food or 17.3% of total lipids. On a per 100 grams of food basis, the highest mean TFA content among the 18 food subgroups was the doughnuts/French toast subgroup (0.95 g), followed by the other pastries subgroup (0.49 g) and the bread with filling/topping subgroup (0.44 g). Among the samples, the highest TFA content is from a doughnut (4.7 g/100 g), followed by two cream-filled bread with shredded coconut (1.8 and 1.4 g/100 g) and a sweetheart cake (1.7 g/100 g). Only consuming one whole piece of doughnut would have reached 100% of the maximum daily TFA intake as recommended by WHO based on a 2000 kcal diet. About 78% of samples had TFA ≤0.3 g/100 g food. For the majority of the food samples available in Hong Kong, if TFA was present, C18:1 trans would possibly be the predominant one.

An open source Java just-in-time (JIT) compiler called LaTTe is introduced that performs fast generation of efficiently register-mapped RSIC code. Experimental results indicate that LaTTe's sophisticated register mapping and allocation achieves twice the performance of a naive JIT compiler that maps all local variables and stack entries to memory.