Search

Background: While Women's Health (WH) is a priority for primary care, (Family Medicine (FM), Internal Medicine (IM), Pediatrics (Peds), and combined Medicine/Pediatrics (Med/Peds)), residency curricula remain heterogeneous with deficits in graduates' WH expertise and skills. The overall objective of this study was to assess the quality of WH curricula at primary care residency programs in the United States (US), with a focus on topics in obstetrics and gynecology (OBGYN). Methods: PubMed®, ERIC, The Cochrane Library, MedEdPORTAL, and professional organization websites were systematically searched in 2019 and updated in 2021. Included studies described OBGYN educational curricula in US primary care residency programs. Following abstract screening and full-text review, data from eligible studies was abstracted and quality assessed using the Medical Education Research Study Quality Instrument (MERSQI). Results: A total of 109 studies met the inclusion criteria. Over a quarter of studies were interdepartmental or interdisciplinary. The most common single-department studies were IM (38%) and FM (26%). Twenty (25%) studies addressed comprehensive OBGYN curricula; the most common individual topics were cervical and breast cancer screening (31%) and contraception (16%). Most studies utilized multiple instructional modalities, most commonly didactics (54%), clinical experiences (41%), and/or simulation (21%). Most studies included self-reported outcomes by residents (70%), with few (11%) reporting higher-level assessments (i.e., patient, or clinical outcomes). Most studies were single-group pre- and post-test (42%) with few randomized controlled trials (4%). The mean MERSQI score for studies with sufficient data (90%) was 9.8 (range 3 to 15.5). Discussion: OBGYN educational curricula for primary care trainees in the US was varied with gaps in represented residents, content, assessments, and study quality. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of the 17‐gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR). Patients and Methods: We designed a case‐cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin‐fixed paraffin‐embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case‐cohort design. Results: In univariable analysis, every 20‐unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11–2.19; P = 0.011). The study is limited by its retrospective and single institution design. Conclusions: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision‐making regarding adjuvant therapy after RP. [ABSTRACT FROM AUTHOR]

El Niño events, the warm phase of the El Niño–Southern Oscillation (ENSO) phenomenon, amplify climate variability throughout the world1. Uncertain climate model predictions limit our ability to assess whether these climatic events could become more extreme under anthropogenic greenhouse warming2. Palaeoclimate records provide estimates of past changes, but it is unclear if they can constrain mechanisms underlying future predictions3–5. Here we uncover a mechanism using numerical simulations that drives consistent changes in response to past and future forcings, allowing model validation against palaeoclimate data. The simulated mechanism is consistent with the dynamics of observed extreme El Niño events, which develop when western Pacific warm pool waters expand rapidly eastwards because of strongly coupled ocean currents and winds6,7. These coupled interactions weaken under glacial conditions because of a deeper mixed layer driven by a stronger Walker circulation. The resulting decrease in ENSO variability and extreme El Niño occurrence is supported by a series of tropical Pacific palaeoceanographic records showing reduced glacial temperature variability within key ENSO-sensitive oceanic regions, including new data from the central equatorial Pacific. The model–data agreement on past variability, together with the consistent mechanism across climatic states, supports the prediction of a shallower mixed layer and weaker Walker circulation driving more frequent extreme El Niño genesis under greenhouse warming.A combination of palaeoclimate proxies and simulations shows that a common mechanism controls El Niño variation in cold and warm states, which supports expectations of more extreme El Niño occurrence in the future. [ABSTRACT FROM AUTHOR]

In this rapid communication, accelerated undergraduate medical education is examined using prior literature as well as experiences of those who have completed or are in the process of completing accelerated medical curricula. The Consortium of Accelerated Medical Pathway Programs (CAMPP) hosts an annual multi-institutional conference for all its members. During the meeting in July 2023, a virtual panel was convened from multiple constituent programs (N = 4) including medical students (N = 2), resident physicians (N = 4), and faculty (N = 2). Panel participants represented current learners or graduates from accelerated pathways of varying specialties (N = 5) to share firsthand experiences about acceleration to an audience representing over 25 medical schools. Five key themes were identified for accelerated students and trainees: Reduced debt as motivating factor to accelerate, Feeling prepared for residency, Ideal accelerated students are driven, Ability to form early professional relationships, and Less time for additional clinical experiences. Discourse from the CAMPP panel can inform current and developing accelerated programs at institutions looking to create or improve accelerated learning. [ABSTRACT FROM AUTHOR]

Numerous high-sensitivity cardiac troponin (hs-cTn) assays for acute myocardial infarction (MI) are available.1,2 These assays differ in their limits of detection, precision, and repeatability.3 The American College of Cardiology and American Heart Association guidelines endorse the 99th percentile upper reference limit for detecting myocardial injury to diagnose acute MI using hs-cTn.4 Evidence of myocardial injury with cardiac symptoms, new electrocardiogram changes, loss of viable myocardium per imaging, or evidence of coronary thrombus on angiography meets diagnostic criteria for acute MI.5 There is no standard cutoff value for hs-cTn. Abnormal values are based on a reference population for individual assays. [ABSTRACT FROM AUTHOR]

There are numerous Neoarchean metasedimentary rock packages in the Slave craton, and they serve as important archives of tectonic processes. Little is documented on the Neoarchean sedimentary packages of the Winter Lake greenstone belt of the central Slave craton, however, and their interpretation can aid in the understanding of the final stages of Slave craton amalgamation. This project investigates the depositional environments and tectonic settings of the Itchen Formation and Sherpa Formation of the Winter Lake greenstone belt. Our study provides constraints for reconstructing the Neoarchean evolution of the central Slave craton through bedrock mapping and facies analysis. The Itchen Formation consists of submature mudstone, siltstone, and sandstone, with preserved graded bedding, planar bedding, and flame structures. Unconformably overlying the Itchen Formation is the Sherpa Formation, which is dominated by polymictic conglomerates and coarse-grained sandstones with preserved cross-bedding, imbricated clasts, and scour surfaces. The Itchen Formation is interpreted to have been deposited in a convergent basin (i.e., retro-arc foreland basin), where two facies associations outline turbidite and suspension sedimentation consistent with submarine fan deposition on a continental slope and a basin floor environment. By contrast, the Sherpa Formation has three facies associations representing dominantly alluvial–fluvial environments in terrestrial–marine–lacustrine settings deposited in pull-apart basins resulting from transtensional forces associated with the Beniah fault zone. [ABSTRACT FROM AUTHOR]

Communication research is increasingly concerned with the relationship between epistemological fragmentation and polarization. Even so, explanations for why partisans take up fringe beliefs are limited. This article examines the right-wing conspiracy QAnon, which posits that the anonymous poster "Q" is a Trump administration insider who encourages followers ("Bakers") to research hidden truths behind current events. Drawing on qualitative fieldwork on the 8chan imageboard, we position baking as a collective, knowledge-making activity built on the affordances of social media designed to construct specific facts and theories that maintain QAnon's cohesion over time. Bakers demonstrate populist expertise, the rejection of legacy media accounts of current events in favor of the "alternative facts" constructed through their systematic research programs. We emphasize the politically ambivalent nature of participatory culture and argue that baking casts doubt on critical thinking or media literacy as solutions to "post-truth" dilemmas like hyperpartisan media and disinformation. [ABSTRACT FROM AUTHOR]

Despite Twitch's dominant position in Western livestreaming markets, institutional journalists rarely produce content on the platform. This paper investigates how journalistic practices, cultures, business models, and institutions approach Twitch through three empirical sites: The Washington Post's experimentation with the app, left-leaning political influencer Hasan Piker, and the pro-QAnon 24/7 "news" channel, Patriots' Soapbox. The cases demonstrate how newsmaking on Twitch flouts traditional journalists' ideological and occupational boundaries, exploiting the platform's features and affordances to enroll the audience in a live broadcasting experience. [ABSTRACT FROM AUTHOR]

Clinical applications of CAR-T cells are limited by the scarcity of tumor-specific targets and are often afflicted with the same on-target/off-tumor toxicities that plague other cancer treatments. A new promising strategy to enforce tumor selectivity is the use of logic-gated, two-receptor systems. One well-described application is termed Tmod™, which originally utilized a blocking inhibitory receptor directed towards HLA-I target antigens to create a protective NOT gate. Here we show that the function of Tmod blockers targeting non-HLA-I antigens is dependent on the height of the blocker antigen and is generally compatible with small, membrane-proximal targets. We compensate for this apparent limitation by incorporating modular hinge units to artificially extend or retract the ligand-binding domains relative to the effector cell surface, thereby modulating Tmod activator and blocker function. By accounting for structural differences between activator and blocker targets, we developed a set of simple geometric parameters for Tmod receptor design that enables targeting of blocker antigens beyond HLA-I, thereby broadening the applications of logicgated cell therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Preclinical drug screening experiments for anti-cancer drug discovery typically involve testing candidate drugs against cancer cell lines. This process can be expensive and time consuming since the possible experimental space can be quite huge, involving all of the combinations of candidate cell lines and drugs. Guiding drug screening experiments with active learning strategies could potentially identify promising candidates for successful experimentation. This study investigates various active learning strategies for selecting experiments to generate response data for identifying effective treatments and improving the performance of drug response prediction models. We have demonstrated that most active learning strategies are more efficient than random selection for identifying effective treatments. It is well-known that cancers of the same histology type can respond differently to a treatment. Thus, computational drug response prediction is of paramount importance for both preclinical drug screening studies and clinical treatment design. To build drug response prediction models, treatment response data need to be generated through screening experiments and used as input to train the prediction models. In this study, we investigate various active learning strategies of selecting experiments to generate response data for the purposes of (1) improving the performance of drug response prediction models built on the data and (2) identifying effective treatments. Here, we focus on constructing drug-specific response prediction models for cancer cell lines. Various approaches have been designed and applied to select cell lines for screening, including a random, greedy, uncertainty, diversity, combination of greedy and uncertainty, sampling-based hybrid, and iteration-based hybrid approach. All of these approaches are evaluated and compared using two criteria: (1) the number of identified hits that are selected experiments validated to be responsive, and (2) the performance of the response prediction model trained on the data of selected experiments. The analysis was conducted for 57 drugs and the results show a significant improvement on identifying hits using active learning approaches compared with the random and greedy sampling method. Active learning approaches also show an improvement on response prediction performance for some of the drugs and analysis runs compared with the greedy sampling method. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology that can involve any organ. Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. Symptoms can present at any age and affect any organ system; however, pulmonary sarcoidosis is the most common. Extrapulmonary manifestations often involve cardiac, neurologic, ocular, and cutaneous systems. Patients with sarcoidosis can exhibit constitutional symptoms such as fever, unintentional weight loss, and fatigue. The early recognition and diagnosis of sarcoidosis are challenging because there is no diagnostic standard for testing, initial symptoms vary, and patients may be asymptomatic. Consensus guidelines recommend a holistic approach when diagnosing sarcoidosis that focuses on clinical presentation and radiographic findings, biopsy with evidence of noncaseating granulomas, involvement of more than one organ system, and elimination of other etiologies of granulomatous disease. Corticosteroids are the initial treatment for active disease, with refractory cases often requiring immunosuppressive or biologic therapies. Transplantation can be considered for advanced and end-stage disease depending on organ involvement. (Am Fam Physician. 2024; 109(1):19–29. Copyright © 2024 American Academy of Family Physicians.) Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown etiology that can involve any organ. Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. Symptoms can present at any age and affect any organ system; however, pulmonary sarcoidosis is the most common. Extrapulmonary manifestations often involve cardiac, neurologic, ocular, and cutaneous systems. Patients with sarcoidosis can exhibit constitutional symptoms such as fever, unintentional weight loss, and fatigue. The early recognition and diagnosis of sarcoidosis are challenging because there is no diagnostic standard for testing, initial symptoms vary, and patients may be asymptomatic. Consensus guidelines recommend a holistic approach when diagnosing sarcoidosis that focuses on clinical presentation and radiographic findings, biopsy with evidence of noncaseating granulomas, involvement of more than one organ system, and elimination of other etiologies of granulomatous disease. Corticosteroids are the initial treatment for active disease, with refractory cases often requiring immunosuppressive or biologic therapies. Transplantation can be considered for advanced and end-stage disease depending on organ involvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Anti-cancer drug response prediction models aim to reduce the time necessary for developing a treatment for patients affected by this complex disease. Their goal is to decrease the number of required biological experiments by computationally weeding out unpromising compounds. In this work, we explore the potential gains of incorporating large-scale applications of classical virtual screening techniques like molecular docking into cutting-edge deep learning models. We demonstrate improvement in performance as well as limitations of our approach. Cancer is a heterogeneous disease in that tumors of the same histology type can respond differently to a treatment. Anti-cancer drug response prediction is of paramount importance for both drug development and patient treatment design. Although various computational methods and data have been used to develop drug response prediction models, it remains a challenging problem due to the complexities of cancer mechanisms and cancer-drug interactions. To better characterize the interaction between cancer and drugs, we investigate the feasibility of integrating computationally derived features of molecular mechanisms of action into prediction models. Specifically, we add docking scores of drug molecules and target proteins in combination with cancer gene expressions and molecular drug descriptors for building response models. The results demonstrate a marginal improvement in drug response prediction performance when adding docking scores as additional features, through tests on large drug screening data. We discuss the limitations of the current approach and provide the research community with a baseline dataset of the large-scale computational docking for anti-cancer drugs. [ABSTRACT FROM AUTHOR]

This paper examines how consumers' body satisfaction, beliefs about the malleability of their appearance, and incidental comparisons with upward vs. lateral social media influencers interact to affect the type of consumption behaviors they engage in. Based on propositions of the compensatory consumption behavior (CCB) model and the social comparison theory, this study employs an online experiment with a 2 (social comparison: upward/lateral) × 2 (body satisfaction: low/high) × 2 (implicit theory: entity/incremental) × 2 (product type: head- and body-related) mixed-factorial design among a sample of 192 women (19–35 years). The appearance of the influencers was manipulated (upward: thinner, primped models; lateral: average weight, natural models), as were the products being advertised, whereas body satisfaction and consumers' implicit theory were measured. The results indicated that consumers were more persuaded to purchase products from lateral compared to upward influencers. Further, lateral influencers were more persuasive for head-related (vs. body-related) products, whereas upward influencers were more successful in promoting body-related (vs. head-related) products. A significant (p < 0.05) interaction between body satisfaction, implicit theory of appearance, and product type also emerged, supporting the proposals of the CCB model on how consumption behaviors are affected by felt discrepancies. These findings indicate that marketers can access more effective marketing results by collaborating with influencers that have a similar appearance to that of their target audience. [ABSTRACT FROM AUTHOR]

Principal Wilson is a first-year leader of a virtual high school. Following four years as an assistant principal in the brick-and-mortar school, she encounters unanticipated leadership challenges and policy dilemmas. Although discipline issues are nearly nonexistent, remote testing presents an ethical challenge. Moreover, she discovers that implementing the tenants of social presence is an unconditional requirement of a virtual school. In this case, the principal faces tough decisions when considering discipline for cheating, the lack of professional development for part-time teachers, and the potential effects of trauma-influenced behavior. This case explores the emerging field of virtual school principal leadership in the context of increasing online K–12 learning post-pandemic. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding of associations between a combination of health behaviors (physical activity, sedentary/screen‐time, diet) and cardiometabolic health risk factors, physical performance, and emotional health among young (<18) childhood cancer survivors (CCS). The aims of this research were to address this gap by 1) deriving health behavior adherence profiles among CCS, and 2) examining associations among demographic, diagnosis and/or treatment exposures, cardiometabolic, physical performance, and emotional functioning with health behavior profile membership. Methods: Participants included 397 CCS (≥5 years post‐diagnosis; 10–17 years old) enrolled in the St. Jude Lifetime Cohort Study who completed physical health evaluations and questionnaires assessing health behaviors and psychological functioning. Latent profile analysis was used to derive profiles of health behavior adherence. Logistic regression and t‐tests were used to examine mean‐level differences and associations between profile membership with demographic, diagnosis, treatment exposures, cardiometabolic health, psychological functioning, and physical performance. Results: Two profiles emerged: inactive‐unhealthy‐diet ("IU") and active‐sedentary‐unhealthy‐diet ("ASU") to guidelines. More participants in IU demonstrated higher resting heart rate (mean [M], 76.54; SD = 12.00) and lower motor proficiency scores (M = 34.73; SD = 29.15) compared to ASU (resting heart rate, M = 71.95, SD = 10.74; motor proficiency, M = 50.40, SD = 31.02). Conclusions: CCS exhibited low adherence to multiple health behavior guidelines, with adherence patterns differentially associated with cardiometabolic health (i.e., resting heart rate) and physical performance. However, robust protection against all health variables was not observed. Findings suggest interventions designed to improve health outcomes should target multiple health behaviors simultaneously. Plain Language Summary: Pediatric cancer survivors are at‐risk for detrimental health outcomes associated with cancer and treatment.Engagement in healthy lifestyle behaviors serves to reduce health vulnerabilities among adult survivors but less is known about associations with lifestyle behaviors on young survivors.This study documents patterns of lifestyle behaviors among survivors of pediatric cancer, factors that increase susceptibility to nonadherence, and associations among lifestyle behaviors and health indicators. Young (<18 years of age) survivors of pediatric cancer exhibit poor adherence to diet and physical activity guidelines. Adherence is associated with clinical health outcomes. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Leeuwenhoek became a fabric merchant and ran a haberdashery in Delft. Topics include course of his work, Leeuwenhoek used a simple microscope to inspect fabrics used in his drapery and clothing business; and Leeuwenhoek's daughter Maria auctioned these items, netting 61 pounds.

Current evidence does not support regular use of AI with breast cancer mammography screening, and family physicians cannot specifically request that it be added. [ABSTRACT FROM AUTHOR]

In recent years, sleep duration has received increased scrutiny with respect to criminologically relevant outcomes. No attention, however, has been given to the possible relationship between sleep duration and the likelihood of arrest. Given the negative downstream effects that arrest may have on adolescents, this is an important relationship to investigate. To this end, the current study uses data from the 2018 Florida Youth Substance Abuse Survey (N=49,360), and the results indicate that severe sleep deficiencies are positively associated with self-reported arrest, whereas minor deficiencies and excess sleep are not. Discussion focuses on the implications and limitations of these findings as well as a call for better integration of health behaviors into criminological analyses. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of object play in animals, including dogs, has been understudied compared to social play behavior. The aims of the present study are to describe the development of a detailed ethogram of object play for dogs that can also be applied to studies of related canids. Moreover, we describe the ontogeny (i.e., the development) of object play in three breeds of domestic dogs from 3–7 weeks of age as they interacted with five different pet toys (objects). Individual behaviors were then categorized into three groups as follows: those that occurred only in the solitary context; those that occurred only in the social context; and those that occurred in both contexts. Theses behavior groups were analyzed for differences across breed and age. Solitary object play developed first, and social object play developed later across breeds. Uncovering early developing breed differences in object play behaviors may aid in understanding both how play develops and the role that selection and domestication has played in the evolution of dogs and their behavioral variability. Play behavior is a prominent aspect of juvenile behavior for many animals, yet early development, especially play with objects, has received little attention. Our previous study on object play introduced our general methods, focusing on litter differences in the developmental trajectory of object play and toy preferences. Here, we present a detailed ethogram of more than 30 observed object play behaviors. We focus on breed differences in the development of play in the three following breeds: Welsh Terriers, Vizslas, and standard Poodles. Puppies were video recorded from 3 to 7 weeks of age at half-week intervals upon the introduction of a standard set of five toys into their home environments. Ten minutes of video from each session for each puppy were analyzed using the Noldus Observer XT program. Aside from analyzing individual behaviors, they were also grouped into three behavioral categories. These were behaviors that occurred only in a solitary context, only in a social context, or in both contexts. Solitary object play developed first, and social object play developed later across breeds. There was a significant three-way interaction between breed, developmental age, and the context in which play occurred. Pairwise comparisons within each breed, age, and context are discussed, but a prominent result is that the onset of many behaviors occurred later in Welsh Terriers compared to the other breeds. [ABSTRACT FROM AUTHOR]

Ratioing describes when a reply earns more likes than an original post on social media. They also offer influencers opportunities to convert audience attention into political actions capable of temporarily shaping online discourse. Ratios are then one of many influencer-driven strategies that leverage platform features and affordances to direct audiences to specific actions that amplify the influencer's content in the crowded social media entertainment market. Hasan Piker is one of the most popular political influencers on Twitch, which he uses as a base to organize and direct his audience into coordinated actions across multiple platforms. Piker reigns on Twitch, but has significantly less Twitter followers than all of his targets, meaning the ratio strategy prompts targeted actions that simultaneously increase his visibility. This article uses three case studies to highlight ratioing as a strategy for eliciting political participation, such as when Piker ratioed rivaling political influencers, a US Senator, and a famous rapper. [ABSTRACT FROM AUTHOR]

Protein-ligand docking is a computational method for identifying drug leads. The method is capable of narrowing a vast library of compounds down to a tractable size for downstream simulation or experimental testing and is widely used in drug discovery. While there has been progress in accelerating scoring of compounds with artificial intelligence, few works have bridged these successes back to the virtual screening community in terms of utility and forward-looking development. We demonstrate the power of high-speed ML models by scoring 1 billion molecules in under a day (50 k predictions per GPU seconds). We showcase a workflow for docking utilizing surrogate AI-based models as a pre-filter to a standard docking workflow. Our workflow is ten times faster at screening a library of compounds than the standard technique, with an error rate less than 0.01% of detecting the underlying best scoring 0.1% of compounds. Our analysis of the speedup explains that another order of magnitude speedup must come from model accuracy rather than computing speed. In order to drive another order of magnitude of acceleration, we share a benchmark dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million "in-stock" molecules over 15 receptors, or binding sites, across the SARS-CoV-2 proteome. We believe this is strong evidence for the community to begin focusing on improving the accuracy of surrogate models to improve the ability to screen massive compound libraries 100 × or even 1000 × faster than current techniques and reduce missing top hits. The technique outlined aims to be a fast drop-in replacement for docking for screening billion-scale molecular libraries. [ABSTRACT FROM AUTHOR]

Protein-ligand docking is a computational method for identifying drug leads. The method is capable of narrowing a vast library of compounds down to a tractable size for downstream simulation or experimental testing and is widely used in drug discovery. While there has been progress in accelerating scoring of compounds with artificial intelligence, few works have bridged these successes back to the virtual screening community in terms of utility and forward-looking development. We demonstrate the power of high-speed ML models by scoring 1 billion molecules in under a day (50 k predictions per GPU seconds). We showcase a workflow for docking utilizing surrogate AI-based models as a pre-filter to a standard docking workflow. Our workflow is ten times faster at screening a library of compounds than the standard technique, with an error rate less than 0.01% of detecting the underlying best scoring 0.1% of compounds. Our analysis of the speedup explains that another order of magnitude speedup must come from model accuracy rather than computing speed. In order to drive another order of magnitude of acceleration, we share a benchmark dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million "in-stock" molecules over 15 receptors, or binding sites, across the SARS-CoV-2 proteome. We believe this is strong evidence for the community to begin focusing on improving the accuracy of surrogate models to improve the ability to screen massive compound libraries 100 × or even 1000 × faster than current techniques and reduce missing top hits. The technique outlined aims to be a fast drop-in replacement for docking for screening billion-scale molecular libraries. [ABSTRACT FROM AUTHOR]

Protein-ligand docking is a computational method for identifying drug leads. The method is capable of narrowing a vast library of compounds down to a tractable size for downstream simulation or experimental testing and is widely used in drug discovery. While there has been progress in accelerating scoring of compounds with artificial intelligence, few works have bridged these successes back to the virtual screening community in terms of utility and forward-looking development. We demonstrate the power of high-speed ML models by scoring 1 billion molecules in under a day (50 k predictions per GPU seconds). We showcase a workflow for docking utilizing surrogate AI-based models as a pre-filter to a standard docking workflow. Our workflow is ten times faster at screening a library of compounds than the standard technique, with an error rate less than 0.01% of detecting the underlying best scoring 0.1% of compounds. Our analysis of the speedup explains that another order of magnitude speedup must come from model accuracy rather than computing speed. In order to drive another order of magnitude of acceleration, we share a benchmark dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million "in-stock" molecules over 15 receptors, or binding sites, across the SARS-CoV-2 proteome. We believe this is strong evidence for the community to begin focusing on improving the accuracy of surrogate models to improve the ability to screen massive compound libraries 100 × or even 1000 × faster than current techniques and reduce missing top hits. The technique outlined aims to be a fast drop-in replacement for docking for screening billion-scale molecular libraries. [ABSTRACT FROM AUTHOR]

New therapies for retinitis pigmentosa (RP) have led to patients desiring more information about their disease. We assessed the readability, content, and accountability of online health information for RP and its treatments. Two internet queries were performed: one pertaining to the condition RP, and another pertaining to treatments of RP. Three analyses were performed on the top search results that met eligibility criteria: (1) A readability analysis produced an average reading level; (2) A content analysis was conducted to score each source on the accuracy, completeness, clarity, and organization of the content; and (3) An accountability analysis was performed to evaluate adherence to accountability benchmarks, including authorship, attribution, disclosure, and currency. The mean reading level was 12.0 (SD = 3.2, 95% CI = 11.0–13.0) for the 8 RP webpages and 12.5 (SD = 3.1, 95% CI = 11.7–13.4) for the 10 RP treatment webpages. The mean content score for RP sites was 21.3 of 32 points (SD = 4.1, 95% CI = 19.5–23.0). The mean content score for RP treatment sites was 5.5 out of 16 points (SD = 3.7, 95% CI = 4.1–6.9). The inter-rater reliability was 0.973 (Cronbach's alpha). For RP sites, the mean accountability score was 2.6 out of 4 points (SD = 0.9, 95% CI = 1.9–3.4). For RP treatment sites, the mean accountability score was 2 out of 4 points (SD = 0.9, 95% CI = 1.4–2.6). Our data suggest that the online information available to patients regarding RP and RP treatment options exceeds the AMA-recommended sixth-grade reading level and contains gaps in content relevant to patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer remains one of the leading causes of death in men in the United States. The commonly utilized method of diagnosing prostate cancer is via the digital rectal examination and serum PSA assay, which is usually followed by biopsy of the prostate gland to evaluate the extent of the cancer. While serum PSA assay has been used for many years by urologists across the globe to diagnose prostate cancer, a falsely elevated level due to conditions (BPH or prostatitis) other than cancer could cause the patient to undergo prostate gland biopsy, which is invasive and poses a greater risk of complications. To overcome these issues, we evaluated whether urinary PSA, which is secreted from the prostate gland into the urine could have predictive value in differentiating aggressive prostate cancer from indolent disease. In this study, we analyzed more than 400 samples for serum and urinary PSA, and found that urinary PSA had a higher predictive power in differentiating aggressive prostate cancer, and could serve a better surrogate tumor biomarker in capitulating the tissue milieus for the purpose of detecting aggressive prostate cancer. Furthermore, combining the ratio between serum to urine PSA enhanced the performance of both biomarkers in predicting aggressive prostate diseases. These studies support the role of urinary PSA, in combination with serum, for detecting aggressive prostate cancer. Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained the gold standard in urological practices for the management of and intervention for prostate cancer. Based on these adopted practices, the limitations of serum PSA in identifying aggressive prostate cancer has led us to evaluate whether urinary PSA levels might have any clinical utility in prostate cancer diagnosis. Utilizing the Access Hybritech PSA assay, we evaluated a total of n = 437 urine specimens from post-DRE prostate cancer patients. In our initial cohort, PSA tests from a total of one hundred and forty-six (n = 146) urine specimens were obtained from patients with aggressive (Gleason Score ≥ 8, n = 76) and non-aggressive (Gleason Score = 6, n = 70) prostate cancer. A second cohort, with a larger set of n = 291 urine samples from patients with aggressive (GS ≥ 7, n = 168) and non-aggressive (GS = 6, n = 123) prostate cancer, was also utilized in our study. Our data demonstrated that patients with aggressive disease had lower levels of urinary PSA compared to the non-aggressive patients, while the serum PSA levels were higher in patients with aggressive prostate disease. The discordance between serum and urine PSA levels was further validated by immuno-histochemistry (IHC) assay in biopsied tumors and in metastatic lesions (n = 62). Our data demonstrated that aggressive prostate cancer was negatively correlated with the PSA in prostate cancer tissues, and, unlike serum PSA, urinary PSA might serve a better surrogate for capitulating tissue milieus to detect aggressive prostate cancer. We further explored the utility of urine PSA as a cancer biomarker, either alone and in combination with serum PSA, and their ratio (serum to urine PSA) to predict disease status. Comparing the AUCs for the urine and serum PSA alone, we found that urinary PSA had a higher predictive power (AUC= 0.732) in detecting aggressive disease. Furthermore, combining the ratios between serum to urine PSA with urine and serum assay enhanced the performance (AUC = 0.811) in predicting aggressive prostate disease. These studies support the role of urinary PSA in combination with serum for detecting aggressive prostate cancer. [ABSTRACT FROM AUTHOR]

The tectonomagmatic history of the early Paleoproterozoic (Siderian) global tectonomagmatic lull (TML; ca. 2.4–2.2 Ga) is poorly known, limiting understanding of lithospheric processes during the Archean to Proterozoic transition. In this study, we identify and describe an unusual ca. 2.4–2.3 Ga postcollisional A-type granite suite associated with orogenic collapse of a continental collision in the middle of the TML. The postcollisional A-type granitoids consist of monzogranite to tonalite intrusions of the North Shore plutonic suite, emplaced during the middle and later stages of the ca. 2.5–2.3 Ga Arrowsmith orogeny, which represents a long-lived accretionary orogen on the northwestern margin of the Archean Rae craton in northern Canada. New laser ablation (LA)-ICP-MS U-Pb zircon age data indicate that the North Shore plutonic suite represents protracted granitic magmatism over ca. 70 My. The new U-Pb ages combined with previous and new LA-MC-ICP-MS Hf isotope and secondary-ion mass spectrometry O isotope zircon data reveal compositional heterogeneities not previously recorded by bulk isotopic methods and require changes to the classification of the granitoids and their role in the Arrowsmith orogeny. Zircon εHf values of the North Shore plutons are consistent with a mixture of juvenile and older crustal components in their sources, but their nonenriched zircon δ18O values are inconsistent with a large supracrustal melt component, precluding an S-type granite parentage. Instead, their trace-element proportions in discrimination diagrams and zircon δ18O values show A-type granite affinities, which are often missed in studies of ancient, poorly defined orogens. Aluminous compositions of the A-type granites are compatible with emplacement in a continent-continent collision, following postcollisional slab break-off and delamination. Postcollisional emplacement of the A-type granites is consistent with other geologic evidence suggesting that subduction beneath the Rae craton margin ceased by 2.4 Ga. [ABSTRACT FROM AUTHOR]

Research has established that individuals lower in self-control are at increased risk of offline criminal victimization due to their proclivity to engage in risky routine activities. While some studies have investigated whether a similar pattern is observed in the online context, additional inquiry into whether the link between low self-control and cybercrime victimization operates indirectly through risky online behavior is warranted given certain measurement and methodological limitations of prior research. Using original data collected on a sample of young adults, we find that the association between low self-control and a variety measure of cybercrime victimization operates entirely and indirectly through a variety measure of risky online behaviors. The implications of this finding for policy and programing are discussed. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the Emory Ophthalmic Genetics Service (EOGS) adopted a hybrid telehealth-based care model, with patients undergoing a tailored panel of ancillary tests in addition to a video telehealth encounter with the EOGS physician. This study evaluates patient satisfaction with this model and effectiveness of these encounters in producing a clinical and genetic diagnosis. A trained interviewer administered a 14-question validated patient satisfaction survey to eligible subjects between October 2020 and April 2021. A mean "favorability index" for patient satisfaction was calculated (maximum score = 5). Rates of ancillary testing, completion of genetic testing, and diagnostic accuracy were also assessed, and compared to results from a control group of EOGS patients that underwent in-person visits. Twenty-one of 33 eligible patients completed the survey. Nine (42.9%) were female, with mean (± SD) age 51.3 ± 13.6 years. The control group was comprised of 49 subjects, predominantly female (71.4%), with mean age 51.5 ± 15.2 years. The mean (range) favorability index was 4.3 (3.1–5.0). Rates of ancillary testing were lower for the telemedicine group vs. the control group: 38.1% vs. 85.7% (p <.001) for electrophysiology; 42.9% vs. 71.4% (p =.03) for perimetry; and 81.0% vs. 95.9% (p =.04) for fundus imaging. Two (11.1%) and 1 (2.8%) (p =.21) subjects in the telehealth and control groups, respectively, did not complete recommended genetic testing. The clinical diagnosis was compatible with the genetic diagnosis in all subjects. Our results suggest high patient satisfaction and diagnostic accuracy with a hybrid telemedicine-based approach for IRD care, despite lower rates of ancillary testing and no in-person examination. [ABSTRACT FROM AUTHOR]

The ubiquitous applications of the Internet of Things (IoT) devices and the increasing computational capabilities of neural networks (NNs) have led to a new era of edge computing and a paradigm known as edge intelligence (EI). With EI, the goal is to maximize the utilization of resources available within an edge device, offloading only the most compute-intensive operations to the cloud. In this article, we propose to leverage the close similarity between the internal architecture of a typical network decoder and an NN for deep learning on decoders. The proposed NN-over-decoder is developed in Verilog and synthesized on field-programmable gate array (FPGA). Based on experimental results, the system exhibits power consumption of the same order of magnitude as a baseline decoder and negligible memory overhead while increasing local hardware utilization, alleviating the high communication load in typical communication devices, and offering scalable multiply–accumulate (MAC)/cycle performance compared with the state of the art. [ABSTRACT FROM AUTHOR]

A new species of bacteria called Emayella augustorita, belonging to the Pasteurellaceae family, has been discovered in France. The family Pasteurellaceae was named after Louis Pasteur, a renowned figure in the history of medicine. The bacteria in this family are commonly found in the mucosal membranes of the mouth, respiratory, and genital tracts and can cause human illnesses. However, further research is needed to fully understand the taxonomy and characteristics of the species within this family. [Extracted from the article]

Purpose: Children diagnosed with craniopharyngioma are vulnerable to adverse health outcomes. Characterization of body mass index (BMI), physical function, and cardiopulmonary fitness in those treated with proton radiotherapy (PRT) will serve to design interventions to improve outcomes. Methods: Ninety-four children with craniopharyngioma completed physical function testing prior to PRT and annually for 5 years. For each outcome, age- and sex-specific z-scores were calculated using normative values. Participants with z-scores > 1.5 or < − 1.5 were classified as impaired. Those with z-scores > 2.0 or < − 2.0 were classified as significantly impaired. Descriptive statistics were used to describe study outcomes and change in prevalence of impairments from 2 to 5 years after treatment. Results: Nearly half of participants [45.2%, 95% confidence interval (CI) 39.4, 51.0] had mean BMI z-scores > 1.5 at baseline, with prevalence increasing to 66.7% (95% CI 61.5, 71.9) at 5 years. More than half of participants (54.2%, 95% CI 48.4, 60.0) had knee extension strength z-scores < − 1.5 at baseline, with prevalence increasing to 81.3% (95% CI 77.7, 84.9) at 5 years. BMI and knee extension strength had the largest proportion of participants impaired at both 2 and 5 years (53.2% and 62.3%, respectively). Resting heart rate had the highest proportion of participants not impaired at 2 years but became impaired at 5 years (26.6%). Conclusions: Children with craniopharyngioma have BMI and fitness abnormalities at diagnosis and continue 5 years after treatment. This cohort may benefit from interventions designed to improve BMI, strength, and resting indicators of cardiopulmonary fitness. [ABSTRACT FROM AUTHOR]

Research regarding the practice of leaders' mindfulness has increased over the past several years. Emphasis on principals' mindfulness practices helped educational leaders become stronger during these uncertain and stressful times. Specifically, researching how principals use mindfulness in a school setting advances educational leadership by exploring this relationship. This systematic review aimed to understand how principals use mindful practices in their schools and relationships with their stakeholders. Attributes of mindfulness used in their leadership practices were explored to influence ways to enhance educational leadership training. Fourteen peer-reviewed research studies from 2010-2021 were reviewed. There were five key themes identified related to a principal's use of mindfulness: (a) school organization, (b) decision-making, (c) well-being, (d) leadership attributes, and (e) student success. This article concluded by discussing the key findings and suggestions to guide future research on principals' mindfulness. [ABSTRACT FROM AUTHOR]

Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future. [ABSTRACT FROM AUTHOR]

In the last 20 years, there has been a sharp increase in the incidence of retractions of articles published in scientific journals, the majority of which are due to research misconduct. In some cases, researchers have revised and republished articles that were retracted due to misconduct, which raises some novel questions concerning authorship. Suppose that an article is retracted because one of the authors fabricated or falsified some data, but the researchers decide to salvage the useable data, make appropriate revisions, and resubmit the article for publication. If the person who committed misconduct has made a significant contribution to the research reported in the revised paper, should they be named as an author to recognize this contribution or should they be denied authorship because they committed misconduct? This is a challenging issue because it involves the confluence of two research ethics domains that are usually dealt with separately, i.e., resolution of authorship disputes and adjudication of misconduct findings, as well as potential conflicts among norms that underlie authorship practices and misconduct adjudication. In this paper, we (1) describe some actual cases involving articles that were retracted for misconduct and republished; (2) review policies from the International Committee of Medical Journal Editors, Committee on Publication Ethics, and top fifteen biomedical journals to determine whether they provide adequate guidance for cases like these; and (3) analyze the ethical and policy issues that may arise in these situations. [ABSTRACT FROM AUTHOR]

Multimodal therapies were combined to eradicate the primary site, metastatic, and micrometastatic disease in men with newly diagnosed, synchronous, oligometastatic prostate cancer. The investigation included companion, phase II studies: total eradication therapy-1 (TET-1) for those treatment-naïve and total eradication therapy-2 (TET-2) for those post-prostatectomy. The treatment-naive protocol included androgen deprivation and docetaxel (with concurrent abiraterone added in a protocol amendment), followed by a prostatectomy, adjuvant radiation (if positive margins, T3/4, or detectable PSA), and metastasis-directed therapy. The post-prostatectomy protocol assigned the same therapies (omitting the prostatectomy). The primary endpoint was an undetectable PSA with recovered testosterone. The safety boundaries were ≤ 50% for grade 3/4 neutropenic and ≤ 20% for grade 3/4 surgical- and radiation-related toxicities. Enrollment was planned for 60 patients per protocol, to detect a PSA progression-free survival ≥ 32%, as compared to 15% in a historic control. Enrollment closed early. An interim analysis was conducted once > 50% of patients were evaluable for the primary endpoint. The primary endpoint duration was assessed by median progression-free survival. 52 patients were enrolled (n = 26 per protocol). Medium follow-up was 30.3 months. 80% (24/30) of evaluable patients achieved the primary endpoint; the duration was not reached. Of those not evaluable, 77% (17/22) had not reached the endpoint and 23% (5/22) had exited. There were 8% (4/52) grade 3/4 neutropenic and 2% (1/48) grade 3/4 surgical or radiation-induced toxicities. Interim findings suggest the trials' endpoints were met, advancing the concept of total eradication therapy in men with oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Multimodal therapies were combined to eradicate the primary site, metastatic, and micrometastatic disease in men with newly diagnosed, synchronous, oligometastatic prostate cancer. The investigation included companion, phase II studies: total eradication therapy-1 (TET-1) for those treatment-naïve and total eradication therapy-2 (TET-2) for those post-prostatectomy. The treatment-naive protocol included androgen deprivation and docetaxel (with concurrent abiraterone added in a protocol amendment), followed by a prostatectomy, adjuvant radiation (if positive margins, T3/4, or detectable PSA), and metastasis-directed therapy. The post-prostatectomy protocol assigned the same therapies (omitting the prostatectomy). The primary endpoint was an undetectable PSA with recovered testosterone. The safety boundaries were ≤ 50% for grade 3/4 neutropenic and ≤ 20% for grade 3/4 surgical- and radiation-related toxicities. Enrollment was planned for 60 patients per protocol, to detect a PSA progression-free survival ≥ 32%, as compared to 15% in a historic control. Enrollment closed early. An interim analysis was conducted once > 50% of patients were evaluable for the primary endpoint. The primary endpoint duration was assessed by median progression-free survival. 52 patients were enrolled (n = 26 per protocol). Medium follow-up was 30.3 months. 80% (24/30) of evaluable patients achieved the primary endpoint; the duration was not reached. Of those not evaluable, 77% (17/22) had not reached the endpoint and 23% (5/22) had exited. There were 8% (4/52) grade 3/4 neutropenic and 2% (1/48) grade 3/4 surgical or radiation-induced toxicities. Interim findings suggest the trials' endpoints were met, advancing the concept of total eradication therapy in men with oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Context: Kidney transplant is superior to dialysis for the treatment of end‐stage kidney disease, but accessing transplant requires high patient engagement to overcome barriers. We sought to develop an educational counselling intervention for patients along with their social support networks to help patients access the waiting list. Methods: Utilizing an Intervention Mapping approach, we established a conceptual framework to develop a behavioural intervention that can be reproduced across kidney transplant centres. The approach includes needs assessment, identifying behavioural determinants and process objectives and integrating targeted behavioural change theory. Results: The Intervention Mapping process resulted in the development of a group counselling session, titled Journey to Transplant (JtT). This intervention was designed for kidney transplant candidates along with members of their social support networks and guided by a transplant healthcare professional. The session begins with standardized educational information to improve knowledge and normalize emotional barriers to transplant. This education is followed by a tailored counselling intervention, including the presentation of the individual patient's calculated likely outcomes on the kidney transplant waiting list. Finally, JtT incorporates patient and support network goal setting to address the specific barriers for that patient in accessing kidney transplantation. Conclusion: A systematic Intervention Mapping approach to develop the JtT intervention helps ensure the intervention is efficacious, acceptable and feasible for transplant centres to implement. JtT engages the patient's social support network, targeting known barriers to transplant and utilizing established behaviour change theory to motivate concrete actions to improve the likelihood of kidney transplantation. Patient or Public Contribution: This study includes a patient and family advisory committee comprised of kidney transplant candidates and their family members to guide the final language and content of the intervention guide, and the conduct of the implementation and pilot testing of the intervention. However, patients and family members were not involved in the intervention mapping development process itself described in this manuscript, which was informed by focus group data from patient and family study participants. [ABSTRACT FROM AUTHOR]

Recent paleoclimate reconstructions have suggested millennial‐scale variability in the Indo‐Pacific Warm Pool region coincident with events of the last deglaciation. Here, we present a new stalagmite oxygen isotope record from northern Borneo, which today is located near the center of the region's mean annual intertropical convergence zone. The record spans the full deglaciation, and reveals for the first time distinct oxygen isotope variations at this location connected with the Bølling‐Allerød onset and the Younger Dryas event. The full deglaciation in the Borneo stalagmite proxy reconstruction appears remarkably similar to a 20–11 ka transient simulation of rainfall over the area produced using the isotope‐enabled Community Earth System Model. In this model, periods of weakened Atlantic Ocean meridional overturning circulation are associated with an anomalous Western North Pacific anticyclone, which is produced in boreal autumn and shifts south over Borneo during boreal winter, causing dry conditions. Plain Language Summary: Here, we aim to resolve conflicting evidence of how tropical convection in Borneo in the Indo‐Pacific oceanic region, a critical region associated with El Niño events and the Asian and Australian‐Indonesian monsoon systems, was affected by past changes in the strength of Atlantic Ocean circulation. Analyzing a 20,000+ year old Borneo cave stalagmite along its growth axis, we find large oxygen isotope shifts coincident with two prominent millennial‐scale periods of reduced Atlantic Ocean overturning circulation strength. The isotope record is similar to a neighboring southwestern Philippine stalagmite record, and we interpret the signal as drier mean annual conditions over the region during these events compared to the background state; an interpretation supported by simulations in three independent state‐of‐the‐art climate models. One model suggests that these conditions in Borneo were driven by the southward shift of an anomalous anticyclone in the boreal winter season. By combining geochemical and model evidence, this study has shown that rainfall decreased for millennial periods during the end of the ice age, when the Atlantic Ocean overturning circulation weakened. In doing so, we have elucidated further how this region responds to major changes in global climate and ocean conditions. Key Points: A new stalagmite record reveals for the first time distinct Bølling‐Allerød and Younger Dryas oxygen isotope variations in northern BorneoThe stalagmite oxygen isotope pattern strongly resembles the recent iCESM transient annual rainfall simulation from 20 to 11 kaBorneo drying during Heinrich 1 and the Younger Dryas may be attributed to an anomalous boreal winter Western North Pacific anticyclone [ABSTRACT FROM AUTHOR]

A machine learning (ML) design framework is proposed for adaptively adjusting clock frequency based on propagation delay of individual instructions. A random forest model is trained to classify propagation delays in real time, utilizing current operation type, current operands, and computation history as ML features. The trained model is implemented in Verilog as an additional pipeline stage within TigerMIPS processor. The modified system is experimentally tested at the gate level in 45 nm CMOS technology, exhibiting simultaneously a speedup of 70 percent and an energy reduction of 30 percent with coarse-grained ML classification as compared with the baseline TigerMIPS. A speedup of 89 percent is demonstrated with finer granularities with a simultaneous 15.5 percent reduction in energy consumption. [ABSTRACT FROM AUTHOR]

Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions. Parathyroid hormone, which is released by the parathyroid glands primarily in response to low calcium levels, stimulates osteoclastic bone resorption and serum calcium elevation, reduces renal calcium clearance, and stimulates intestinal calcium absorption through synthesis of 1,25-dihydroxyvitamin D. Primary hyperparathyroidism, in which calcium levels are elevated without appropriate suppression of parathyroid hormone levels, is the most common cause of hypercalcemia and is often managed surgically. Indications for parathyroidectomy in primary hyperparathyroidism include presence of symptoms, age 50 years or younger, serum calcium level more than 1 mg per dL above the upper limit of normal, osteoporosis, creatinine clearance less than 60 mL per minute per 1.73 m2, nephrolithiasis, nephrocalcinosis, and hypercalciuria. Secondary hyperparathyroidism is caused by alterations in calcium, phosphate, and vitamin D regulation that result in elevated parathyroid hormone levels. It most commonly occurs with chronic kidney disease and vitamin D deficiency, and less commonly with gastrointestinal conditions that impair calcium absorption. Secondary hyperparathyroidism can be managed with calcium and vitamin D replacement and reduction of high phosphate levels. There is limited evidence for the use of calcimimetics and vitamin D analogues for persistently elevated parathyroid hormone levels. Hypoparathyroidism, which is most commonly caused by iatrogenic surgical destruction of the parathyroid glands, is less common and results in hypocalcemia. Multiple endocrine neoplasia types 1 and 2A are rare familial syndromes that can result in primary hyperparathyroidism and warrant genetic testing of family members, whereas parathyroid cancer is a rare finding in patients with hyperparathyroidism. [ABSTRACT FROM AUTHOR]

To enable personalized cancer treatment, machine learning models have been developed to predict drug response as a function of tumor and drug features. However, most algorithm development efforts have relied on cross-validation within a single study to assess model accuracy. While an essential first step, cross-validation within a biological data set typically provides an overly optimistic estimate of the prediction performance on independent test sets. To provide a more rigorous assessment of model generalizability between different studies, we use machine learning to analyze five publicly available cell line-based data sets: National Cancer Institute 60, ancer Therapeutics Response Portal (CTRP), Genomics of Drug Sensitivity in Cancer, Cancer Cell Line Encyclopedia and Genentech Cell Line Screening Initiative (gCSI). Based on observed experimental variability across studies, we explore estimates of prediction upper bounds. We report performance results of a variety of machine learning models, with a multitasking deep neural network achieving the best cross-study generalizability. By multiple measures, models trained on CTRP yield the most accurate predictions on the remaining testing data, and gCSI is the most predictable among the cell line data sets included in this study. With these experiments and further simulations on partial data, two lessons emerge: (1) differences in viability assays can limit model generalizability across studies and (2) drug diversity, more than tumor diversity, is crucial for raising model generalizability in preclinical screening. [ABSTRACT FROM AUTHOR]

Although self-recognition or self-awareness has been studied with the visually-based mirror test, passed by several species, primarily apes, the possibility of a chemically-based analogue is controversial. Prior studies suggested that chemical self-recognition may occur in some squamate reptiles. To evaluate this possibility, we studied 24 individually housed gartersnakes, Thamnophis sirtalis , raised from birth on either earthworm or fish diets and tested 12 male and 12 female snakes with cage liners that were either clean, their own, or from same-sex siblings fed their own or the opposite diet. Tongue flicking and activity were recorded in 30-minute video-recorded trials in a balanced design. After initial habituation to the stimuli, male, but not female, snakes discriminated between their own stimuli and those from littermates fed the same diet. Combined with other data and studies, the possibility that a chemical 'mirror' form of self-recognition exists in squamate reptiles is supported. [ABSTRACT FROM AUTHOR]

Background: Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail.Methods: Frailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates.Results: Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32).Conclusions: Prevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors. [ABSTRACT FROM AUTHOR]