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Subterranean structures such as aquifers and depleted gas reservoirs (DGRs) offer a scalable, high-pressure, secure, cost-efficient, and ecologically friendly means of hydrogen (H 2) storage. Underground H 2 storage (UHS) has emerged as a potential solution to alleviate the imbalance between the fluctuating renewable energy generation and the demand for a constant energy supply. Quantifying the recovery efficiency is of paramount importance in the effort toward large-scale UHS. In this numerical simulation study, we employed a high-resolution grid for the discretization of a synthetic (but realistic) heterogeneous anticline intended as a H 2 storage facility, and we assessed the H 2 recovery efficiency, and the purity of produced gas associated with UHS in natural reservoirs involving different pre-existing gases and their quantities. All of these studies included an initial phase of cushion gas injection, followed by 4 cycles of H 2 storage operations composed of injection-idle-withdrawal periods. The simulation results indicated that the H 2 round-trip recovery efficiency R H increased (a) with an increasing number of storage cycles, routinely exceeding 90% and providing evidence of a self-enhancement or self-optimization H 2 recovery mechanism and (b) with an increasing amount of pre-existing gas in the storage zone prior to the H 2 injections — at the end of the 4-cycle test, the highest R H is associated with a DGR with a pre-existing gas consisting of residual CH 4 and additional injected N 2 , and the lowest R H corresponds to an aquifer with no cushion gas. Conversely, the H 2 mass fraction of the produced gas F HQ (a) increased with an increasing number of storage cycles, but (b) decreased rapidly with an increasing amount of pre-existing gas. The presence of a pre-existing gas inevitably leads to severe contamination of the produced H 2 , which never exceeds 40% in the produced gas, can be as low as 4% in early cycles, and cannot be used as a H 2 fuel without gas separation. Aquifer storage without a cushion gas may exhibit the lowest H 2 recovery (about 75% in the long run), but yields practically pure H 2 that does not require further processing before use. A positive conclusion is that, under the conditions of this study, total H 2 losses (including H 2 escaping into the caprock, and inaccessible H 2 dissolved in the aqueous phase of the formation or remaining in the gas storage zone) are limited and manageable, indicating the technical feasibility of geologic H 2 storage. • Discussed the advantages and disadvantages of H 2 storage (UHS) in aquifers and depleted gas reservoirs (DGRs). • Explained reasons for the benefits of cushion gas (CG) or DGRs in UHS performance using material balance theory. • Injecting CG or adding cycles enhances the UHS performance by improving the overall compressibility of reservoirs. • Pre-existing gas improves the H 2 recovery efficiency but leads to the contamination of produced H 2. • Quantified the H 2 loss evolution during a UHS consisting of four injection-idle-withdrawal cycles. [ABSTRACT FROM AUTHOR]

Conversations about race in South Africa continue to be shaped by a religious-redemptive narrative of reconciliation that emerged in the democratic transition. However, there is a history of critical Black and liberation theological voices questioning whether the religious/ethical ideal of reconciliation adequately addresses the injustices of systemic racism. These questions gained new resonance in recent years with social movements like #feesmustfall. This article asks whether the seemingly intractable hope that a theological concept of reconciliation will be efficacious in facilitating racial justice is warranted. We begin by reviewing and interrogating how reconciliation is being used in contemporary theological discourses, arguing that given rising discontent, it is striking that reconciliation continues to be a prominent theme and topic within South African Christian theological discourses. We then propose several alternatives that may help address the problem of white racism and benefit from the sustained energy that South African theology has been putting into the language of reconciliation. [ABSTRACT FROM AUTHOR]

Courts rely heavily on the recommendations of mental health evaluators when making decisions about competency (e.g., Zapf, Hubbard, Cooper, Wheeles, & Ronan, 2004), including civil competency (e.g., Quickel, Demakis, & Reeve, 2017); however, very little is known about how evaluators arrive at their opinions regarding an individual's capacity. The current study assessed clinical decision-making using a policy capturing methodology. An ecologically valid sample (N = 47) of predominantly white (87.23%) and female (55.30%) clinicians who were eligible to conduct civil competency evaluations in North Carolina were recruited to examine the degree to which five key factors (functional test data, cognitive test data, personality test data, hospitalization history, and/or medication compliance) influenced clinician competency determinations. Personal insight into one's decision-making process was also measured. Consistent with previous research, functional test data was weighted most heavily in evaluator decisions, though all five factors were considered. Further analysis suggested variable levels of self-awareness of one's decision-making policies by participants depending on the factor. In addition, there was high agreement among clinicians when cases were straightforward, but perfect disagreement (half recommending competency, half recommending incompetency) among clinicians when cases were more complex. Implications for civil competency assessment and decision-making are discussed. IMPACT STATEMENT: Functional assessment data drives clinician decisions regarding civil capacity, over and above the impact of cognitive and personality test data, hospitalization history, and medication compliance. Due to high levels of court reliance on the recommendation of clinical evaluators, and the different standards of civil competency across different states and jurisdictions, understanding how evaluators arrive at competency recommendations is imperative and has clinical, legal, and ethical implications. [ABSTRACT FROM AUTHOR]

We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed. [ABSTRACT FROM AUTHOR]

The racial gap in infant mortality is a pressing public-health concern, and [B. N. Greenwood et al., Proc. Natl. Acad. Sci. U.S.A. 117, 21194-21200 (2020), 10.1073/pnas.1913405117] suggest that Black newborns are more likely to survive if cared for by Black physicians after birth, even in models that control for numerous variables, including hospital and physician fixed effects, and the 65 most common comorbidities affecting newborns (as described by International Classification of Disease codes). We acquired the data used in the study, covering Florida hospital discharges from 1992 through the third quarter of 2015, to replicate and extend the analysis. We find that the magnitude of the concordance effect is substantially reduced after controlling for diagnoses indicating very low birth weight (<1,500 g), which are a strong predictor of neonatal mortality but not among the 65 most common comorbidities. In fact, the estimated effect is near zero and statistically insignificant in the expanded specifications that control for very low birth weight and include hospital and physician fixed effects. [ABSTRACT FROM AUTHOR]

The constellation approach underpinning precipitation products such as the Integrated Multi‐satellitE Retrievals for GPM (IMERG) is key to achieving high resolution, but the use of data from multiple sources can unintentionally incorporate instrumental artifacts. Here, we introduce a machine learning–based anomaly detection scheme called SPEEDe, which processes a two‐dimensional precipitation field into a re‐estimated precipitation field that can be compared with the input. Large differences identify IMERG fields with bad orbit data, separating most of the bad cases from the good cases. When modified to process the passive microwave inputs, SPEEDe can pick out orbits with bad data, enabling quality control on these IMERG inputs. SPEEDe works by producing a locally realistic‐looking precipitation field when given unphysical data, which results in a larger‐than‐normal difference between the input and the output. SPEEDe is implemented as an automated quality control for GPM precipitation products. Plain Language Summary: A machine learning–based scheme, SPEEDe, has been developed to identify bad data in satellite precipitation products. This scheme is able to pick out precipitation maps that have unrealistic patterns better than a conventional approach based on the distribution of values. It can be run as the precipitation data are being produced, thus allowing for automated quality control. Avoiding manual intervention is important in computing quality‐controlled precipitation data in near‐real time for applications such as flood monitoring that require highly reliable data with minimal delay. Key Points: A machine learning scheme called SPEEDe can detect artifacts in satellite precipitation fields based on an aggregate grid‐wide scoreSPEEDe identifies bad data by modifying anomalous inputs substantially to produce realistic‐looking outputs, leading to a large scoreSPEEDe is being applied operationally in GPM data production for quality control [ABSTRACT FROM AUTHOR]

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ -lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future. [ABSTRACT FROM AUTHOR]

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 μM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 μM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation. [ABSTRACT FROM AUTHOR]

The paper addresses rare issue in cable ampacity calculations, namely the presence of discontinuities along the routes. One which occurs in almost all cable installations is the presence of joints. In a standard cable rating analysis, the joints are ignored, mostly because of difficulties in building analytical models that represent the heat transfer phenomena within them. However, they can be a limiting part of the cable rating and, therefore, there is a need to model them correctly. This paper introduces an analytical algorithm for cable rating calculations in the presence of discontinuities with an emphasis on cable joints. New developments are illustrated by several numerical examples. [ABSTRACT FROM AUTHOR]

Intestinal transplantation is a complex technical procedure that provides patients suffering from end-stage intestinal failure an opportunity to enjoy improved quality of life, nutrition and survival. Compared to other types of organ transplants, it is a relatively new advancement in the field of organ transplantation. Nevertheless, great advances have been made over the past few decades to the present era, including the use of ischemic preconditioning, gene therapy, and addition of pharmacological supplements to preservation solutions. However, despite these strides, intestinal transplantation is still a challenging endeavor due to several factors. Notable among them is ischemia-reperfusion injury (IRI), which results in loss of cellular integrity and mucosal barrier function. In addition, IRI causes graft failure, delayed graft function, and decreased graft and recipient survival. This has necessitated the search for novel therapeutic avenues and improved transplantation protocols to prevent or attenuate intestinal IRI. Among the many candidate agents that are being investigated to combat IRI and its associated complications, nitric oxide (NO). NO is an endogenously produced gaseous signaling molecule with several therapeutic properties. The purpose of this mini-review is to discuss IRI and its related complications in intestinal transplantation, and NO as an emerging pharmacological tool against this challenging pathological condition. i • Cold preservation and engraftment induces ischemia-reperfusion injury IRI. • Nitric oxide produced by iNOS exerts detrimental effect on intestinal grafts. • Nitric oxide donors protect intestinal grafts against IRI and associated complications. • Nitric oxide prevents acute graft rejection after intestinal transplantation. • Endogenous nitric oxide protects intestinal mucosal barrier function. [ABSTRACT FROM AUTHOR]

Excessive hip adduction and internal rotation are common movement impairments associated with patellofemoral pain (PFP). As such, strengthening of the hip abductors and external rotators commonly is recommended. Because tensor fascia latae (TFL) is a hip internal rotator in addition to being an abductor, it is important to select exercises that target the superior gluteus maximus (SUP-GMAX) and gluteus medius (GMED) while minimizing activation of the TFL. To identify hip-targeted exercises resulting in greater activation of the SUP-GMAX and GMED relative to the TFL in persons with PFP. Twelve individuals with PFP participated. Electromyographic (EMG) signals were obtained from the GMED, SUP-GMAX, and TFL using fine-wire electrodes while participants performed 11 hip-targeted exercises. Normalized EMG of GMED and SUP-GMAX was compared to that of the TFL for each exercise using repeated measures ANOVAs and descriptive statistics. Of the 11 hip exercises evaluated, only the clam exercise with elastic resistance resulted in significantly greater activity of both gluteal muscles (SUP-GMAX = 24.2 ± 14.4%MVIC, p =.05; GMED = 37.2 ± 19.7%MVIC, p =.008) relative to the TFL (12.5 ± 11.7%MVIC). Five exercises exhibited significantly lower activation of SUP-GMAX relative to TFL: 1) unilateral bridge: SUP-GMAX = 17.7 ± 9.8%MVIC, TFL = 34.0 ± 17.7%MVIC, p =.01; 2) bilateral bridge: SUP-GMAX = 10.0 ± 6.9%MVIC, TFL = 14.0 ± 7.5%MVIC, p =.04; 3) abduction: SUP-GMAX = 14.2 ± 11.1%MVIC, TFL = 33.0 ± 11.9%MVIC, p =.001; 4) hip hike: SUP-GMAX = 14.8 ± 12.8%MVIC, TFL = 46.8 ± 33.7%MVIC, p =.008; and 5) step-up: SUP-GMAX = 15.0 ± 5.4%MVIC, TFL = 31.7 ± 19.9 %MVIC, p =.02). No differences in gluteal activation relative to TFL were found for the remaining 6 exercises (all p >.05). The clam with elastic resistance exercise was effective at activating the SUP-GMAX and GMED greater than TFL. No other exercises achieved a similar level of muscular recruitment. When attempting to strengthen the gluteal muscles in persons with PFP, care should be taken in assuming that common hip-targeted exercises result in the desired recruitment patterns. [ABSTRACT FROM AUTHOR]

Simple Summary: Plexiform neurofibromas in neurofibromatosis type 1 (pNF1), characterized by aggressive growth and local invasiveness, are comprised primarily of Schwann cell-derived tumor cells (Nf1−/−) and the tumor microenvironment (TME). Fibroblasts (Nf1+/−), the most abundant cell type in the TME, are known to significantly contribute to pNF1 formation, but their precise role in the subsequent tumor progression is poorly understood. Using our established three-dimensional (3D) culture models with patient-derived pNF1 cells and fibroblasts, we observed that the fibroblast-derived secretome stimulates the growth and local invasiveness of pNF1 spheroids. Depletion of small extracellular vesicles (sEVs) from the fibroblast secretome completely eliminated the paracrine effect on pNF1 spheroid growth. These results suggest that targeting paracrine interactions between pNF1 tumor cells and fibroblasts may offer a potential therapeutic approach for reducing pNF1 tumor progression. Plexiform neurofibromas (PNs) occur in about a half of neurofibromatosis type 1 (NF1) patients and have garnered significant research attention due to their capacity for growth and potential for malignant transformation. NF1 plexiform neurofibroma (pNF1) is a complex tumor composed of Schwann cell-derived tumor cells (Nf1−/−) and the tumor microenvironment (TME). Although it has been widely demonstrated that the TME is involved in the formation of neurofibromas, little is known about the effects of the TME on the subsequent progression of human pNF1. Elucidating the molecular interactions between tumor cells and the TME may provide new therapeutic targets to reduce the progression of pNF1. In the present study, we focused on the contributions of fibroblasts, the most abundant cell types in the TME, to the growth of pNF1. To simulate the TME, we used a three-dimensional (3D) coculture model of immortalized pNF1 tumor cells (Nf1−/−) and primary fibroblasts (Nf1+/−) derived from pNF1 patients. We performed live-cell imaging of 3D/4D (3D in real-time) cultures through confocal microscopy followed by 3D quantitative analyses using advanced imaging software. The growth of pNF1 spheroids in 3D cocultures with fibroblasts was significantly greater than that of pNF1 spheroids in 3D monocultures. An increase in the growth of pNF1 spheroids also occurred when they were cultured with conditioned media (CM) from fibroblasts. Moreover, fibroblast-derived CM increased the invasive outgrowth and further local invasion of pNF1 spheroids. Interestingly, when small extracellular vesicles (sEVs) were depleted from the fibroblast-derived CM, the stimulation of the growth of pNF1 spheroids was lost. Our results suggest that fibroblast-derived sEVs are a therapeutic target for reducing the growth of pNF1. [ABSTRACT FROM AUTHOR]

Although synapsins have long been proposed to be key regulators of synaptic vesicle (SV) clustering, their mechanism of action has remained mysterious and somewhat controversial. Here, we review synapsins and their associations with each other and with SVs. We highlight the recent hypothesis that synapsin tetramerization is a mechanism for SV clustering. This hypothesis, which aligns with numerous experimental results, suggests that the larger size of synapsin tetramers, in comparison to dimers, allows tetramers to form optimal bridges between SVs that overcome the repulsive force associated with the negatively charged membrane of SVs and allow synapsins to form a reserve pool of SVs within presynaptic terminals. [ABSTRACT FROM AUTHOR]

This article discusses a case of narrow complex tachycardia with alternating atrial activation. The patient had previously undergone an ablation procedure for pre-excited atrial fibrillation but experienced recurrent episodes of palpitations. The article explores the mechanism behind the alternating atrial activation and suggests that it may be due to conduction block across the mitral isthmus. The left lateral pathway was successfully ablated, resulting in the resolution of the tachycardia. Further research and mapping techniques are recommended to improve the accuracy of ablation procedures. [Extracted from the article]

• Most high school students with ADHD improve functioning with training intervention. • Improvement most likely for adolescents with better pre-treatment functioning. • Multiple malleable factors (e.g., dosage) increase likelihood of improved functioning. • Some students may require additional school-based services with training intervention. Adolescents with attention-deficit/hyperactivity disorder (ADHD) experience significant academic, behavioral, and social skill difficulties including underachievement, risk for school dropout, poor peer relations, and emotion dysregulation. Although stimulant medication reduces ADHD symptoms, psychosocial and educational interventions are necessary to address functional impairments. We examined the nature and predictors of academic, behavioral, and social skills trajectories in response to multicomponent organizational and interpersonal skills training in 92 high school students with ADHD. Latent trajectory class analyses revealed positive treatment response ranging from 61.5% (report card grades) to 100% (inattention symptoms, organizational skills, social skills). Organizational skill and academic grade treatment response trajectories were predicted by assigned sex, pretreatment anxiety, and treatment dosage, while improvement in behavioral and social functioning was associated with better emotion regulation and family relations prior to treatment along with stronger working alliance with treatment coach at midtreatment. Multicomponent organizational and interpersonal skills training appears effective for most high school students with ADHD and the degree treatment-induced change is associated with multiple malleable factors can be leveraged to enhance intervention response. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose. [ABSTRACT FROM AUTHOR]

Background: Postoperative ileus (POI) is a common complication after colorectal surgery, leading to increased hospital stay and costs. This study aimed to explore patient comorbidities that contribute to the development of POI in the colorectal surgical population and compare machine learning (ML) model accuracy to existing risk instruments. Study Design: In a retrospective study, data were collected on 316 adult patients who underwent colorectal surgery from January 2020 to December 2021. The study excluded patients undergoing multi-visceral resections, re-operations, or combined primary and metastatic resections. Patients lacking follow-up within 90 days after surgery were also excluded. Eight different ML models were trained and cross-validated using 29 patient comorbidities and four comorbidity risk indices (ASA Status, NSQIP, CCI, and ECI). Results: The study found that 6.33% of patients experienced POI. Age, BMI, gender, kidney disease, anemia, arrhythmia, rheumatoid arthritis, and NSQIP score were identified as significant predictors of POI. The ML models with the greatest accuracy were AdaBoost tuned with grid search (94.2%) and XG Boost tuned with grid search (85.2%). Conclusions: This study suggests that ML models can predict the risk of POI with high accuracy and may offer a new frontier in early detection and intervention for postoperative outcome optimization. ML models can greatly improve the prediction and prevention of POI in colorectal surgery patients, which can lead to improved patient outcomes and reduced healthcare costs. Further research is required to validate and assess the replicability of these results. [ABSTRACT FROM AUTHOR]

Context: Typically, most clinical return to activity guidelines recommend that an injured shoulder achieve a 90% to 100% functional performance test limb symmetry index (LSI); however, as previous research demonstrated a 103% to 111% dominant limb bias in seated single-arm shot-put test (SSASPT) performance, the typical criteria might not be appropriate for interpreting SSASPT LSI. Thus, the current objective was to evaluate SSASP LSI differences between dominant and nondominant involved shoulders and to determine how many patients met the suggested 90% to 100% LSI criteria, as well as the 103% for dominant (89% for nondominant) normative SSASPT threshold reported in the literature, at the time of discharge. Design: Cross-sectional. Methods: Patients with shoulder injury or surgery (n = 78) completed the SSASPT at the time of discharge from rehabilitation and were grouped according to whether the involved shoulder was the dominant (n = 42) or nondominant (n = 32) limb. LSI (involved/uninvolved × 100) was computed from the average of 3 SSASPT trial distances completed with each limb. Results: The LSI for the nondominant involved group (88.9% [12.4%]) was significantly less (confidence intervalDiff, −12.1% to −22.1%) than the dominant involved group (106.0% [9.3%]). While 95.2% of patients in the dominant involved group exhibited LSI > 90%, only 43.8% of patients in the nondominant involved group attained LSI > 90%. Across the entire cohort, the odds of a nondominant involved LSI being below the respective SSASPT normative range were 2.04 (95% confidence interval, 0.80–5.21) times higher than the odds of a dominant involved LSI being below the normative range. Conclusions: Patients with dominant limb involvement exhibited higher LSI than patients with nondominant limb involvement at discharge from rehabilitation. Particularly when the nondominant shoulder is involved, these results suggest that patients with shoulder injury and surgery may require longer rehabilitation to attain higher levels of upper-extremity function. [ABSTRACT FROM AUTHOR]

Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3‐aminoazetidine (3‐AAz) subunit as a new turn‐inducing element for the efficient synthesis of small head‐to‐tail cyclic peptides. Greatly improved cyclizations of tetra‐, penta‐ and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Post‐cyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained four‐membered azetidine. A special feature of this chemistry is that further late‐stage modification of the resultant macrocyclic peptides can be achieved via the 3‐AAz unit. This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a click‐based approach employing a 2‐propynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, all‐trans conformation. Moreover, introduction of a 3‐AAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle. [ABSTRACT FROM AUTHOR]

Ribosomal DNA (rDNA), which encodes ribosomal RNA, is an essential but unstable genomic element due to its tandemly repeated nature. rDNA's repetitive nature causes spontaneous intrachromatid recombination, leading to copy number (CN) reduction, which must be counteracted by a mechanism that recovers CN to sustain cells' viability. Akin to telomere maintenance, rDNA maintenance is particularly important in cell types that proliferate for an extended time period, most notably in the germline that passes the genome through generations. In Drosophila, the process of rDNA CN recovery, known as 'rDNA magnification', has been studied extensively. rDNA magnification is mediated by unequal sister chromatid exchange (USCE), which generates a sister chromatid that gains the rDNA CN by stealing copies from its sister. However, much remains elusive regarding how germ cells sense rDNA CN to decide when to initiate magnification, and how germ cells balance between the need to generate DNA double-strand breaks (DSBs) to trigger USCE vs. avoiding harmful DSBs. Recently, we identified an rDNA-binding Zinc-finger protein Indra as a factor required for rDNA magnification, however, the underlying mechanism of action remains unknown. Here we show that Indra is a negative regulator of rDNA magnification, balancing the need of rDNA magnification and repression of dangerous DSBs. Mechanistically, we show that Indra is a repressor of RNA polymerase II (Pol II)-dependent transcription of rDNA: Under low rDNA CN conditions, Indra protein amount is downregulated, leading to Pol II-mediated transcription of rDNA. This results in the expression of rDNA-specific retrotransposon, R2, which we have shown to facilitate rDNA magnification via generation of DBSs at rDNA. We propose that differential use of Pol I and Pol II plays a critical role in regulating rDNA CN expansion only when it is necessary. Author summary: Ribosomal DNA (rDNA) exists as tandemly-repeated copies in eukaryotic genome, making it unstable due to spontaneous intrachromatid recombination that causes copy number loss. The germline, which is the sole cell type that transmits genome from generation to generation, must expand rDNA copy number to counteract spontaneous copy number loss. It has been shown that the process of rDNA copy number expansion, called rDNA magnification, involves rDNA binding protein Indra and retrotransposon R2. However, the underlying molecular mechanism of rDNA magnification and how Indra and R2 may functionally intersect remained unknown. This study shows that Indra is a transcriptional repressor of the intergenic spacer (IGS) sequence of rDNA, orchestrating R2 expression and rDNA copy number expression. Low rDNA copy number downregulates Indra, leading to expression of IGS, which in turn leads to expression of R2. It was found that IGS expression is mediated by RNA polymerase II, which is specifically recruited to nucleolus upon rDNA copy number reduction. Together, the results lead to a model how rDNA copy number reduction triggers the process of rDNA copy number expansion. [ABSTRACT FROM AUTHOR]

Acetylsalicylic acid or aspirin is the most commonly used drug in the world and is taken daily by millions of people. There is increasing evidence that chronic administration of low-dose aspirin of about 75–100 mg/day can cause iron deficiency anaemia (IDA) in the absence of major gastric bleeding; this is found in a large number of about 20% otherwise healthy elderly (>65 years) individuals. The mechanisms of the cause of IDA in this category of individuals are still largely unknown. Evidence is presented suggesting that a likely cause of IDA in this category of aspirin users is the chelation activity and increased excretion of iron caused by aspirin chelating metabolites (ACMs). It is estimated that 90% of oral aspirin is metabolized into about 70% of the ACMs salicyluric acid, salicylic acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid. All ACMs have a high affinity for binding iron and ability to mobilize iron from different iron pools, causing an overall net increase in iron excretion and altering iron balance. Interestingly, 2,3-dihydroxybenzoic acid has been previously tested in iron-loaded thalassaemia patients, leading to substantial increases in iron excretion. The daily administration of low-dose aspirin for long-term periods is likely to enhance the overall iron excretion in small increments each time due to the combined iron mobilization effect of the ACM. In particular, IDA is likely to occur mainly in populations such as elderly vegetarian adults with meals low in iron content. Furthermore, IDA may be exacerbated by the combinations of ACM with other dietary components, which can prevent iron absorption and enhance iron excretion. Overall, aspirin is acting as a chelating pro-drug similar to dexrazoxane, and the ACM as combination chelation therapy. Iron balance, pharmacological, and other studies on the interaction of iron and aspirin, as well as ACM, are likely to shed more light on the mechanism of IDA. Similar mechanisms of iron chelation through ACM may also be implicated in patient improvements observed in cancer, neurodegenerative, and other disease categories when treated long-term with daily aspirin. In particular, the role of aspirin and ACM in iron metabolism and free radical pathology includes ferroptosis, and may identify other missing links in the therapeutic effects of aspirin in many more diseases. It is suggested that aspirin is the first non-chelating drug described to cause IDA through its ACM metabolites. The therapeutic, pharmacological, toxicological and other implications of aspirin are incomplete without taking into consideration the iron binding and other effects of the ACM. [ABSTRACT FROM AUTHOR]

We evaluated the extent to which receiving the multi-component treatment of the Challenging Horizons Program (CHP) would lead to significant improvements in social functioning, as well as in inattention, internalizing symptoms, parent stress, and emotion dysregulation for high-school-aged adolescents with attention-deficit hyperactivity disorder (ADHD). Participants were 186 high-school-aged adolescents (74% White) with a diagnosis of ADHD who were randomly assigned to either CHP (n = 92; 80% boys; M age = 15.0; SD = 0.8) or Community Care (CC; n = 94; 78% boys; M age = 15.1; SD = 0.9) within each of 12 participating schools. Parent and adolescent reports of social functioning were the primary outcome measures. Secondary outcomes included ratings of symptoms of ADHD and related disorders, parent stress, and emotion regulation. Intent-to-treat analyses using hierarchical linear modeling revealed significant group-by-time interactions of medium magnitude (d range =.40 to.52) on parent-rated social skills. Significant group-by-time benefits were also identified for adolescent self-rated social skills as well as the secondary outcomes of parent-rated inattention symptoms, emotion regulation, and parenting stress. CHP appears to benefit social skills along with related characteristics for adolescents with ADHD. Understanding these unique findings for this population informs additional research related to treatment mechanisms and effectiveness trials. [ABSTRACT FROM AUTHOR]

Objectives: Early maladaptive schemas represent unhelpful frameworks of cognitions, emotions and subsequent behavioural responses and can be associated with depressive symptoms. Caregivers of individuals with serious mental illness (SMI) frequently report experiencing depressive symptoms. It is unclear whether depressive symptoms in caregivers are influenced by schemas. We aimed to compare activated schemas in caregivers of people with schizophrenia spectrum (SSD) and bipolar disorder (BD) diagnoses and to determine whether they were differentially related to depressive symptoms. Design and Methods: Caregivers completed validated measures of depression and schemas. Independent samples t‐tests and multivariate generalised linear models were used to assess differences in schemas and depressive symptoms between caregiver groups. Interrelationships between schema domains and caregiver depressive symptoms were delineated using correlational analyses and forward stepwise regressions. Results: One hundred eight caregivers participated in the study (SSD n = 68, BD n = 40). No differences in depressive symptom severity or activated schemas were observed between caregiver groups. All schemas were significantly associated with depressive symptoms, and the Disconnection‐Rejection schema domain explained the most variance in depressive symptoms in both caregiver groups. Conclusions: Schemas contribute to the severity of caregiver depression regardless of whether the person receiving care is diagnosed with SSD or BD. Schema therapeutic frameworks may be beneficial for use with caregivers to address schemas within the Disconnection‐Rejection domain and alleviate depressive symptoms by reducing experiences of social isolation and alienation. [ABSTRACT FROM AUTHOR]

We analyse the radio-to-submillimetre spectral energy distribution (SED) for the central pseudo-bulge of NGC 1365 using archival data from the Atacama Large Millimeter/submillimeter Array (ALMA) and the Very Large Array. This analysis shows that free–free emission dominates the continuum emission at 50–120 GHz and produces about 75 per cent of the 103 GHz continuum emission. However, the fraction of 103 GHz continuum emission originating from free–free emission varies significantly among different subregions in the pseudo-bulge, particularly for an outflow from the active galactic nuclei (AGN) on the eastern pseudo-bulge where the synchrotron emission produces half of the 103 GHz continuum emission. Free–free emission also dominates at 103 GHz within the central 400 pc diameter region, but this emission is associated with the AGN rather than star formation. The star formation rate (SFR) within the pseudo-bulge derived from the ALMA free–free emission is 8.9 ± 1.1 M⊙ yr−1. This is comparable to the SFR from the mid-infrared emission but higher than the SFR from the extinction-corrected H α line emission, mainly because the pseudo-bulge is heavily dust obscured. The 1.5 GHz emission yields a comparable SFR for the pseudo-bulge but may have lower SFRs within subregions of the pseudo-bulge because of the diffusion outside of these regions of the electrons producing the synchrotron radiation. We propose that applying a correction factor of 75 per cent to the 80–110 GHz continuum emission could provide valuable estimates of the free–free emission without performing any SED decomposition, which could derive extinction-free SFRs within 20 per cent accuracy. [ABSTRACT FROM AUTHOR]

The supply and control of iron is essential for all cells and vital for many physiological processes. All functions and activities of iron are expressed in conjunction with iron-binding molecules. For example, natural chelators such as transferrin and chelator–iron complexes such as haem play major roles in iron metabolism and human physiology. Similarly, the mainstay treatments of the most common diseases of iron metabolism, namely iron deficiency anaemia and iron overload, involve many iron–chelator complexes and the iron-chelating drugs deferiprone (L1), deferoxamine (DF) and deferasirox. Endogenous chelators such as citric acid and glutathione and exogenous chelators such as ascorbic acid also play important roles in iron metabolism and iron homeostasis. Recent advances in the treatment of iron deficiency anaemia with effective iron complexes such as the ferric iron tri-maltol complex (feraccru or accrufer) and the effective treatment of transfusional iron overload using L1 and L1/DF combinations have decreased associated mortality and morbidity and also improved the quality of life of millions of patients. Many other chelating drugs such as ciclopirox, dexrazoxane and EDTA are used daily by millions of patients in other diseases. Similarly, many other drugs or their metabolites with iron-chelation capacity such as hydroxyurea, tetracyclines, anthracyclines and aspirin, as well as dietary molecules such as gallic acid, caffeic acid, quercetin, ellagic acid, maltol and many other phytochelators, are known to interact with iron and affect iron metabolism and related diseases. Different interactions are also observed in the presence of essential, xenobiotic, diagnostic and theranostic metal ions competing with iron. Clinical trials using L1 in Parkinson's, Alzheimer's and other neurodegenerative diseases, as well as HIV and other infections, cancer, diabetic nephropathy and anaemia of inflammation, highlight the importance of chelation therapy in many other clinical conditions. The proposed use of iron chelators for modulating ferroptosis signifies a new era in the design of new therapeutic chelation strategies in many other diseases. The introduction of artificial intelligence guidance for optimal chelation therapeutic outcomes in personalised medicine is expected to increase further the impact of chelation in medicine, as well as the survival and quality of life of millions of patients with iron metabolic disorders and also other diseases. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify out-of-hospital cardiac arrest characteristics for patients treated by collegiate-based emergency medical services (CBEMS) organizations. CBEMS organizations provided data via the National Collegiate EMS Foundation Cardiac Arrest Data Registry. CBEMS organization details, patient demographics, cardiac arrest characteristics and treatments, and prehospital outcomes for cases spanning October 2007 to May 2020 were analyzed with descriptive statistics. There were 65 OHCA entries. The majority were for male patients (82%) and a notable number of cases occurred in patients 45 years of age or younger (41%). Cases were frequently witnessed (71%) with high rates of bystander cardiopulmonary resuscitation (57%) and defibrillation (29%) prior to EMS arrival. Almost half of the patients (48%) had achieved return of spontaneous circulation until care was transferred to a provider of equal/higher level. CBEMS organizations may be well situated to respond rapidly to on-campus OHCAs. [ABSTRACT FROM AUTHOR]

The current protocol used to determine if an individual is osteoporotic relies on assessment of the individual's bone mineral density (BMD), which allows clinicians to judge the condition of a patient with respect to their peers. This, in essence, evaluates a person's fracture risk, because BMD is a good surrogate measure for strength and stiffness. In recent studies, the authors were the first to produce fracture toughness (FT) data from osteoporotic (OP) and osteoarthritic (OA) patients, by using a testing technique which basically analyzes the prerequisite stress conditions for the onset of growth of a major crack through cancellous bone tissue. FT depends mainly on bone quantity (BV/TV, bone volume/tissue volume), but also on bone micro-architecture (mArch), the inner trabecular design of the bone. The working research hypothesis of the present study is that mArch offers added prediction power to BV/TV in determining FT parameters. Consequently, our aim was to investigate the use of predictive models for fracture toughness and also to investigate if there are any significant differences between the models produced from samples loaded across (AC, transverse to) the main trabecular orientation and along (AL, in parallel) the trabeculae. In multilinear regression analysis, we found that the strength of the relationships varied for a crack growing in these two orthogonal directions. Adding mArch variables in the Ac direction helped to increase the R2 to 0.798. However, in the AL direction, adding the mArch parameters did not add any predictive power to using BV/TV alone; BV/TV on its own could produce R2 = 0.730. The present results also imply that the anisotropic layout of the trabeculae makes it more difficult for a major crack to grow transversely across them. Cancellous bone models and remodels itself in a certain way to resist fracture in a specific direction, and thus, we should be mindful that architectural quality as well as bone quantity are needed to understand the resistance to fracture. [ABSTRACT FROM AUTHOR]

Radiologists are frequently called on for guidance regarding return to play (RTP) for athletes and active individuals after sustaining a musculoskeletal injury. Avoidance of reinjury is of particular importance throughout the rehabilitative process and following resumption of competitive activity. Understanding reinjury risk estimation, imaging patterns, and correlation of clinical and surgical findings will help prepare the radiologist to identify reinjuries correctly on diagnostic imaging studies and optimize management for a safe RTP. [ABSTRACT FROM AUTHOR]

Calls to decolonize education systems cannot be removed from broader social struggles. Scholars have engaged in theoretical discussions on what decolonization entails, emphasizing the need for transforming thoughts, beliefs, and practices. However, the lack of sustained engagement and widespread resistance to decolonizing the curriculum remain evident, underscoring the urgency to envision new futures and explore relationalities between educators and students. In this article, we delve into the evolving terminologies surrounding decolonization, anticolonization, and Indigenization, emphasizing their pivotal roles in the broader project of educational decolonization. We argue that a reassertion of Indigenous resistance and futurity in higher education forms the cornerstone of this transformative process. Through an examination and understanding of these terminologies, we aim to contribute to the ongoing dialogue surrounding educational decolonization and envision inclusive, equitable, and anticolonial learning environments that centre on Indigenous knowledge and perspectives. [ABSTRACT FROM AUTHOR]

The article focuses on the collective trauma experienced during the Covid-19 pandemic and the need for communal remembrance. Topics discussed include the psychological and social impact of prolonged stress; the varying experiences of loss among different communities; and the potential healing power of public commemorations, such as a moment of silence, to help society process and move beyond the shared trauma.

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia–reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia–reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications. [ABSTRACT FROM AUTHOR]

Objective: Negative urgency (NU) and distress tolerance (DT) are two similar yet distinct constructs with putative transdiagnostic relevance, particularly across psychopathology characterized by impulsivity (e.g., substance use disorders [SUD], eating disorders featuring binging and/or purging ED‐B/P, and borderline personality disorder [BPD]). Yet, there remains a lack of research into NU and DT across SUD, ED‐B/P, and BPD symptomatology in clinical populations. The present study sought to elucidate the transdiagnostic utility of NU and DT across impulsive‐type psychology by examining the unique and interactive roles of NU and DT across SUD, ED‐B/P, and BPD symptomatology within a treatment‐seeking sample of young people. Method: Participants (N = 385; 62.3% female; aged 16–25 years) were recruited from youth health services across Melbourne, Australia. Participants completed an online survey including self‐report measures of NU and DT as well as SUD, ED‐B/P, and BPD symptoms. Mixed effects logistic regression was used to explore unique and interactive associations of NU and DT with symptoms. Results: Both NU (adjusted odds ratio [ORadj] = 1.22; 95% confidence interval [CI] = [1.16, 1.28]) and global DT (ORadj = 0.59; 95% CI = [0.47, 0.74]) uniquely predicted symptoms. However, associations with global DT and most of its components differed across psychopathology types. No significant interactions between NU and DT in predicting symptoms were found. Conclusions: These results support the transdiagnostic utility of NU across SUD, ED‐B/P, and BPD, while suggesting the role of DT across these disorders is more nuanced. These findings have important implications for NU and DT as potential intervention targets. [ABSTRACT FROM AUTHOR]

To adjust the decision criterion for the Word Memory Test (WMT, Green, 2003) to minimize the frequency of false positives. Archival data were combined into a database (n = 3,210) to examine the best cut score for the WMT. We compared results based on the original scoring rules and those based on adjusted scoring rules using a criterion based on 16 performance validity tests (PVTs) exclusive of the WMT. Cutoffs based on peer-reviewed publications and test manuals were used. The resulting PVT composite was considered the best estimate of validity status. We focused on a specificity of.90 with a false-positive rate of less than.10 across multiple samples. Each examinee was administered the WMT, as well as on average 5.5 (SD = 2.5) other PVTs. Based on the original scoring rules of the WMT, 31.8% of examinees failed. Using a single failure on the criterion PVT (C-PVT), the base rate of failure was 45.9%. When requiring two or more failures on the C-PVT, the failure rate dropped to 22.8%. Applying a contingency analysis (i.e., X2) to the two failures model on the C-PVT measure and using the original rules for the WMT resulted in only 65.3% agreement. However, using our adjusted rules for the WMT, which consisted of relying on only the IR and DR WMT subtest scores with a cutoff of 77.5%, agreement between the adjusted and the C-PVT criterion equaled 80.8%, for an improvement of 12.1% identified. The adjustmeny resulted in a 49.2% reduction in false positives while preserving a sensitivity of 53.6%. The specificity for the new rules was 88.8%, for a false positive rate of 11.2%. Results supported lowering of the cut score for correct responding from 82.5% to 77.5% correct. We also recommend discontinuing the use of the Consistency subtest score in the determination of WMT failure. [ABSTRACT FROM AUTHOR]

Stress, anxiety and depression, often linked to internalizing/externalizing behaviors, are remarkedly high in a jail-based setting when one's future is uncertain. While research demonstrates that carceral yoga programs can provide physiological/psychological benefits, persons who are incarcerated, who have high rates of trauma-related experiences and mental illness, might benefit more from a trauma sensitive approach. Empirical studies examining the specific impact of trauma sensitive yoga (TSY) on populations who are incarcerated appear unavailable, necessitating this exploratory investigation with male residents in a TSY intervention at a New York jail. Through pre and post-test interviewing and a mixed methods data analysis, data indicated that those who participated in TSY experienced statistically significant increases in overall health, in addition to statistically significant reductions in stress, anxiety, depression and institutional misconduct. Qualitative analyses suggested that male participants experienced transcendence of the jail environment, easing the monotony of the correctional setting. TSY also provided them with new opportunities, the ability to regulate emotions/behaviors and initiate personal growth/changes within. Hence, this research implies that TSY, a benign intervention, easily implemented in a correctional setting, has the ability to beget benefits for persons who are incarcerated within a short period of time. This is vital to providing rehabilitative options within the transient nature of the jail setting. [ABSTRACT FROM AUTHOR]

In this paper, we prove the well‐posedness of a nonlinear wave equation coupled with boundary conditions of Dirichlet and acoustic type imposed on disjoints open boundary subsets. The proposed nonlinear equation models small vertical vibrations of an elastic medium with weak internal damping and a general nonlinear term. We also prove the exponential decay of the energy associated with the problem. Our results extend the ones obtained in previous results to allow weak internal dampings and removing the dimensional restriction 1≤n≤4$$ 1\le n\le 4 $$. The method we use is based on a finite‐dimensional approach by combining the Faedo‐Galerkin method with suitable energy estimates and multiplier techniques. [ABSTRACT FROM AUTHOR]

The article discusses the ongoing challenges and unanswered questions surrounding the COVID-19 pandemic and the need for preparedness for future pandemics. It highlights the current strategies against COVID-19, including vaccination and antiviral drug treatments. The article also mentions various drawbacks and complications in the response to the pandemic, such as the lack of coordination among countries, disparities in access to therapeutics, and delays in regulatory approval. It emphasizes the importance of prevention and transmission reduction strategies, as well as the need for a long-term multilevel drug strategy and a global health system approach. [Extracted from the article]

Strengthening of the hip abductors has been advocated for persons with patellofemoral pain (PFP). It is not clear if these individuals activate the hip abductor muscles appropriately to achieve the desired therapeutic effects. To compare activation of the hip abductor muscles between persons with and without PFP during the performance of hip abductor exercises. Thirty-two individuals participated (12 with PFP and 20 without PFP). The average age (± standard deviation) was 29.7 ± 5.9 years for the PFP group and 28.1 ± 6.9 for the control group. Electromyographic (EMG) signals from the gluteus medius (GMED), superior gluteus maximus (SUP-GMAX), and tensor fascia lata (TFL) were obtained using fine-wire electrodes while participants performed 11 different exercises. Normalized EMG activity of each muscle was compared between groups across all exercises. When averaged across all exercises, persons with PFP exhibited significantly greater EMG activity of TFL (mean = 25.3% MVIC; 95% CI = 19.2, 31.3) compared to those without PFP (mean = 17.6% MVIC; 95% CI = 12.8, 22.4) and significantly lower EMG activity of SUP-GMAX (mean = 16.4% MVIC; 95% CI = 11.0, 22.0) compared to those without PFP (mean = 25.4% MVIC; 95% CI = 21.0, 29.8). Persons with PFP exhibited lower EMG activity of GMED, but only for 3 out of the 11 exercises evaluated (hip abduction, hip hike, step-up). Compared to persons without PFP, those with PFP exhibited activation differences during the performance of exercises used to target the hip abductors. Our results highlight the need for activation training prior to the initiation of strengthening exercises to achieve desired therapeutic effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 10–15% of patients with epithelial ovarian cancer have an inherited (germline) BRCA1 or BRCA2 mutation. Following a diagnosis of epithelial ovarian cancer, patients are routinely tested for germline and/or somatic (tumour) BRCA1/2 mutations. Our study shows that if germline BRCA1/2 testing is only performed for patients with a positive tumour BRCA1/2 test result, and tumour testing is performed using Myriad's myChoice® companion diagnostic, a proportion of germline BRCA1/2 large rearrangements could be missed. If paired germline-tumour DNA testing is not possible for all patients, our data shows that it would be appropriate to test all patients with epithelial ovarian cancer aged < 79 years old for germline BRCA1/2 mutations, regardless of the tumour BRCA1/2 result, whilst only needing to test patients aged ≥ 80 years old for a germline BRCA1/2 mutation if they have a positive tumour BRCA1/2 result. Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice® companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice® CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice® CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged < 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant. [ABSTRACT FROM AUTHOR]

The onset of pregnancy places additional stress of the thyroid gland, which must produce additional thyroid hormones to support the developing foetus. Hypothyroidism, including subclinical hypothyroidism (SCH), may appear de novo at this time, or existing thyroid disease may become more severe. Accordingly, SCH is a relatively common complication of up to about 3% of pregnancies, with higher rates in some areas. There is strong evidence from systematic reviews and meta-analyses that uncontrolled SCH is associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preeclampsia, and gestational diabetes. The evidence base also suggests that treatment with levothyroxine (LT4), optimized to control thyrotropin (TSH) to within its pregnancy-specific reference ranges reduces these risks. Current management guidelines provide a clear framework of intervention with LT4 in pregnant women with SCH, especially where TSH is high or where thyroperoxidase autoantibodies are present. Sub-optimal adherence to LT4 is common: it is important that patients take their LT4 correctly and that treating physicians and/or healthcare professionals manage these patients according to the latest management guidelines. The titration of LT4 is likely to occur within a range of LT4 daily doses between 25 µg and 75 µg for the majority of this population. LT4 is a narrow therapeutic index drug and small variations in dosage may produce a clinically significant change in thyroid status. Newer formulations of LT4, engineered to provide more precise and consistent dosing, and with a broad range of tablet strengths, may facilitate the precise titration of the LT4 dose for these patients. [ABSTRACT FROM AUTHOR]

Background: In children with chronic kidney disease (CKD), certain risk factors are associated with faster eGFR decline and earlier kidney failure. Whether these factors have lingering effects on post-transplant eGFR trajectory remains unclear. We characterized pre- and post-transplant eGFR trajectories in pediatric kidney transplant recipients by their pre-kidney replacement therapy (KRT) risk factors. Methods: We studied eGFR trajectories before KRT initiation and after transplantation among Chronic Kidney Disease in Children (CKiD) Study participants. We used mixed-effects models to compare pre-KRT versus post-transplant eGFR trajectories within individual participants by 7 pre-KRT risk factors: glomerular/non-glomerular etiology, race, preemptive transplant, proteinuria, albuminuria, and systolic/diastolic blood pressure (SBP/DBP). Results: We analyzed 1602 pre-KRT and 592 post-transplant eGFR measurements from 246 transplant recipients. Mean annual eGFR decline was decreased from 18.0% pre-KRT (95%CI, 16.1–19.8) to 5.0% post-transplant (95%CI, 3.3–6.7). All 7 pre-KRT risk factors showed strong associations with faster pre-KRT eGFR decline, but not with post-transplant eGFR decline; only albuminuria, high SBP, and high DBP reached statistical significance with notably attenuated associations. In our multivariable model of the pre-KRT risk factors, post-transplant eGFR decline was more rapid only when albuminuria and high SBP were both present. Conclusions: eGFR decline substantially slows down after transplant even among children with rapidly progressing forms of CKD. Nonetheless, those who had albuminuria and high SBP before KRT might continue to show faster eGFR decline after transplant, specifically when both risk factors were present. This subgroup might benefit from intensive pre-transplant management for at least one of the two risk factors. [ABSTRACT FROM AUTHOR]

This study evaluates the techno-economic feasibility of integrating fuel cells into stand-alone power generation systems, combined with different technologies such as diesel generators, wind turbines, and batteries. An optimisation analysis was performed using the Hybrid Optimization Model for Multiple Energy Resources (HOMER) software to minimise energy costs and several system architectures were obtained for different operating scenarios. The performance and cash flow of the selected system were included. The results suggest that the combination of traditional technologies for fuel cell power generation could be feasible for a country like Colombia, depending on economic factors such as the Consumer Price Index (CPI), the discount rate, and the availability of renewable resources. The proposed system achieves a Levelized Cost of Electricity (LCOE) of $0.112/kWh, comparable to state-of-the-art systems in the literature. This research contributes to the global effort of transitioning to alternative energy sources and reducing carbon emissions. [ABSTRACT FROM AUTHOR]

The design of clinical protocols and the selection of drugs with appropriate posology are critical parameters for therapeutic outcomes. Optimal therapeutic protocols could ideally be designed in all diseases including for millions of patients affected by excess iron deposition (EID) toxicity based on personalised medicine parameters, as well as many variations and limitations. EID is an adverse prognostic factor for all diseases and especially for millions of chronically red-blood-cell-transfused patients. Differences in iron chelation therapy posology cause disappointing results in neurodegenerative diseases at low doses, but lifesaving outcomes in thalassemia major (TM) when using higher doses. In particular, the transformation of TM from a fatal to a chronic disease has been achieved using effective doses of oral deferiprone (L1), which improved compliance and cleared excess toxic iron from the heart associated with increased mortality in TM. Furthermore, effective L1 and L1/deferoxamine combination posology resulted in the complete elimination of EID and the maintenance of normal iron store levels in TM. The selection of effective chelation protocols has been monitored by MRI T2* diagnosis for EID levels in different organs. Millions of other iron-loaded patients with sickle cell anemia, myelodysplasia and haemopoietic stem cell transplantation, or non-iron-loaded categories with EID in different organs could also benefit from such chelation therapy advances. Drawbacks of chelation therapy include drug toxicity in some patients and also the wide use of suboptimal chelation protocols, resulting in ineffective therapies. Drug metabolic effects, and interactions with other metals, drugs and dietary molecules also affected iron chelation therapy. Drug selection and the identification of effective or optimal dose protocols are essential for positive therapeutic outcomes in the use of chelating drugs in TM and other iron-loaded and non-iron-loaded conditions, as well as general iron toxicity. [ABSTRACT FROM AUTHOR]

The unstable supply of renewable energy due to seasonal dependency contradicts the periodic energy demand. As hydrogen presents high energy density and flow mobility, and low solubility and residual saturation, underground hydrogen storage (UHS) is a promising solution of scalable energy storage to rebalance energy demand and supply. Depleted gas reservoirs (DGR) are a suitable option for UHS due to their demonstrated integrity. In this study, we developed a numerical simulation model based on Tough + RealGasBrine (T + RGB) simulator to evaluate the feasibility of UHS in DGR. We calibrated different Equation-of-State (EOS) models for modeling the phase behavior of hydrogen-included mixtures with experimental data, and this further helps to examine the impact of various cushion gas pre-injection strategies on pressure maintenance and potential hydrogen leakage through cap-rock. After comparison among three EOS models, we adopted the Soave-Redlich-Kwong (SRK) EOS in our simulations as its high accuracy and computational efficiency. Afterward, we simulated one hydrogen injection-idle-withdrawal operation in a high-resolution mesh based on a synthetic heterogeneous anticline DGR. We observed that hydrogen displaces pre-existing methane and resides at the top of the storage zone due to gravity segregation. The average pressure and gas saturation of the whole simulation domain increase with the hydrogen injection. With regard to the hydrogen leakage, when the cap-rock permeability ranges from 10 − 5 to 10 − 3 mD, 0.05% of the injected hydrogen at maximum leaks into the cap-rock while about 1% of injected hydrogen is dissolved into the aqueous phase. Those results demonstrate that DGR is a viable option for UHS. However, only about 73% of injected hydrogen can be recovered if the bottom-hole pressure of the production well is 2 MPa below the reservoir pressure. The cushion gas becomes necessary for the UHS project to increase hydrogen recovery. Injecting cushion gas of nitrogen and carbon dioxide increases hydrogen recovery from the initial 73%–91% and 81%, respectively. The simulation results demonstrate that nitrogen exhibits better performance, in terms of higher hydrogen recovery factor and purity of producing gas, as the cushion gas. In this work, we quantitatively evaluated the hydrogen leakage problem, including leakage into cap-rock, dissolution in water, and mixing with other gas components, which is the first-of-its-kind analysis in literature to the author's best knowledge. The simulation results support the feasibility of UHS in the DGR. • Reservoir properties' evolution during the underground H 2 storage is presented via high-resolution simulations. • Hydrogen loss associated with leakage and dissolution are quantitatively identified. • Performance of the cushion gases, including nitrogen and carbon dioxide, is evaluated. [ABSTRACT FROM AUTHOR]

Documented presently as growing wild within, and immediately adjacent to, the Naples Botanical Garden (Collier Co., Florida) are individuals of 115 families, 351 genera, 576 species, and 587 infrageneric taxa of vascular plants. Of the 587 infrageneric taxa documented presently, 414 (70.6%) are clearly native and 13 (2.2%) are endemic to Florida. Herein, seven main kinds of habitats are recognized for the study area, and individual taxa inhabit one or more of those habitats. Seventeen presently reported infrageneric taxa are listed as Endangered (nine taxa) or Threatened (eight taxa) in Florida, and seven are listed as Critically Imperiled in South Florida. Based on the present study and on previous field work undertaken at the study site, 32 species plus two varieties are newly reported for Collier County. [ABSTRACT FROM AUTHOR]

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of 85.69- and 99.02-GHz continuum emission and H42α and H40α lines emission from the central 1 kpc of NGC 1808. These forms of emission are tracers of photoionizing stars but unaffected by dust obscuration that we use to test the applicability of other commonly star formation metrics. An analysis of the spectral energy distributions shows that free–free emission contributes about 60–90 per cent of the continuum emission in the 85–100-GHz frequency range, dependent on the region. The star formation rate (SFR) derived from the ALMA free–free emission is 3.1 ± 0.3 M⊙ yr−1. This is comparable to the SFRs measured from the infrared emission, mainly because most of the bolometric energy from the heavily obscured region is emitted as infrared emission. The radio 1.5-GHz emission yields an SFR 25 per cent lower than the ALMA value, probably because of the diffusion of the electrons producing the synchrotron emission beyond the star-forming regions. The SFRs measured from the extinction-corrected H α line emission are about 40–65 per cent of the SFR derived from the ALMA data, likely because this metric was not calibrated for high-extinction regions. Some SFRs based on extinction-corrected ultraviolet emission are similar to those from ALMA and infrared data, but given that the ultraviolet terms in the extinction correction equations are very small, these metrics seem inappropriate to apply to this dusty starburst. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of postoperative periprosthetic fracture has been reported to be higher in polished tapered femoral stems with the CPT stem possibly of greatest concern. We report on the patient and surgical factors in a consecutive cohort of 2892 CPT stems implanted as part of a total hip construct, either electively or for the treatment of a fractured neck of femur (NOF) over a 15-year period. Methods: The Bluespier departmental database was used to identify any patients who been treated for a Vancouver B periprosthetic fracture around a CPT stem from 2008 to 2021. Patient demographics, mechanism of injury and fracture type were recorded. X-rays were reviewed to identify technical issues that may have contributed to the fracture. Results: A total of 70 fractures were treated. For elective cases the fracture rate was 1.52% while for stems implanted for treatment of a neck of femur fracture (NOF) it was 2.86%. There was a male preponderance and almost all fractures were low energy. The majority (52.9%) were B1 fractures. Only 8 (11.4%) involved a truly loose construct (B2L). The presence of an undersized and varus stem increased the risk of fracture particularly in the NOF population. Discussion: The results in this series are consistent with the registry data regarding the rate of failure of the CPT stem related to periprosthetic fracture. The patient population is typical of those who sustain a proximal femoral fracture in terms of age although we report a male preponderance. The importance of surgical technique in the placement of a correctly sized and aligned stem, particularly in those patients undergoing hip replacement for a neck of femur fracture is highlighted. [ABSTRACT FROM AUTHOR]

The present study sought to identify differences in the rates and predictors of risky sexual behavior among college students with and without attention-deficit hyperactivity disorder (ADHD). Current ADHD diagnosis, medication status among those with ADHD, executive functioning, substance use, comorbid anxiety, comorbid depression, and gender were identified as potential predictors of increased risky sexual behavior. Multiple group latent growth curve modeling was used to estimate trajectories of risky sexual behavior across four years of college among college students with ADHD (nmedicated = 99, nunmedicated = 105) and a comparison group (n = 217) recruited from colleges throughout the eastern United States (M age = 18.23 years, 53% female, 70% White). First-year college students with ADHD reported significantly higher rates of sexual risk behavior than their peers without ADHD, with no significant differences found based on medication status. Students with ADHD who were taking medication for ADHD reported significant decreases in risky sexual behavior over time. Among college students with ADHD, anxiety was related to increased current risky sexual behavior in the medicated group, while depression was predictive of decreased future risky sexual behavior in the unmedicated group. Alcohol and cannabis use were significantly associated with increased mean levels of risky sexual behavior across all three groups, and cannabis use was associated with decreased future risky sexual behavior within the comparison group. Executive functioning deficits and male gender were predictive of risky sexual behavior within the comparison group. The results demonstrate that college students with ADHD, regardless of medication status, are at an increased likelihood of engaging in risky sexual behavior. [ABSTRACT FROM AUTHOR]

The Global Precipitation Climatology Project (GPCP) Version 3.2 Precipitation Analysis provides globally complete analyses of surface precipitation on a 0.5° × 0.5° latitude–longitude grid at both monthly and daily time scales, covering from 1983 to the present and from June 2000 to the present, respectively. These merged products continue the GPCP heritage of incorporating precipitation estimates from low-orbit satellite microwave data, geosynchronous-orbit satellite infrared data, sounder-based estimates, and surface rain gauge observations emphasizing the strengths of various inputs and striving for time and space homogeneity. Furthermore, these analyses incorporate modern algorithms, refined intercalibrations among sensors, climatologies of recent high-quality satellite precipitation data, and fine-scale multisatellite estimates. New data fields have been introduced to better characterize the precipitation, including the fraction of the precipitation that is liquid (rain) in both the monthly and daily products, and a quality index for the monthly product. Compared to the operational GPCP Version 2.3 Monthly, the Version 3.2 Monthly product provides a more reasonable climatology in the Southern Ocean and increases the estimated global average precipitation by about 4.5%, which is similar to estimates from recent global water budget assessments. Global and regional trends for 1983–2020 with this new Monthly dataset are very similar to those computed from Version 2.3. Compared to the operational One-Degree Daily (Version 1.3) product, the new Version 3.2 Daily is designed to better represent the histogram of precipitation rates, particularly at high values and shifts the start of less-certain high-latitude estimates from 40° to 58° latitude in each hemisphere. Significance Statement: Studies of Earth's climate require long-term global datasets based on observations to show how the climate functions and to validate numerical climate models. This study describes an important upgrade to the monthly and daily precipitation (rain and snow) products computed by the Global Precipitation Climatology Project. We use modern analysis schemes, add new sources of data, and deliver results on a finer-scale 0.5° × 0.5° latitude–longitude grid [roughly 55 km (34 mi) on a side at the equator]. The new data show improved agreement with other studies and depict more reasonable behavior in the Southern Ocean. The daily product shows improved estimates of how often different intensities of precipitation occur around the world, particularly the high amounts that drive floods and landslides. [ABSTRACT FROM AUTHOR]

Maternal and paternal perinatal depression and anxiety are theorised to adversely impact infant development. Yet, few studies have assessed both mental health symptoms and clinical diagnoses within the one study. Moreover, research on fathers is limited. This study therefore aimed to examine the association between symptoms and diagnoses of maternal and paternal perinatal depression and anxiety with infant development. Data were from the Triple B Pregnancy Cohort Study. Participants included 1539 mothers and 793 partners. Depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale and Depression Anxiety Stress Scales. Major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia were assessed using the Composite International Diagnostic Interview in trimester three. Infant development was assessed at 12-months using the Bayley Scales of Infant and Toddler Development. Antepartum, maternal depressive and anxiety symptoms were associated with poorer infant social-emotional (d = −0.11, p =.025) and language development (d = −0.16, p =.001). At 8-weeks postpartum, maternal anxiety symptoms were associated with poorer overall development (d = −0.11, p =.030). No association was observed for clinical diagnoses in mothers, nor paternal depressive and anxiety symptoms or clinical diagnoses; albeit risk estimates were largely in the expected direction of adverse effects on infant development. Evidence suggests that maternal perinatal depression and anxiety symptoms may adversely impact infant development. Effects were small but findings underscore the importance of prevention, early screening and intervention, alongside consideration of other risk factors during early critical periods. • Parental perinatal depression and anxiety are theorised to adversely impact infant development. • Few studies have assessed symptoms and clinical diagnoses in the same study, and research on fathers is limited. • Maternal depression and anxiety symptoms predicted poorer infant social-emotional, language, and global development. • No associations were observed for clinical diagnoses in mothers, nor paternal symptoms or clinical diagnoses. • Maternal perinatal mental illness is a risk factor for poorer infant development, underscoring the importance of preventative intervention. [ABSTRACT FROM AUTHOR]

Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia (GA) and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of GA. In order to identify potential phosphorylation events in the brain-mediating GA effects, we have explored the phosphoproteome responses in the rat SON and compared these to cingulate cortex (CC) which displays no FOS activation in response to general anaesthetics. Methods: Adult Sprague-Dawley rats were treated with isoflurane for 15 min. Proteins from the CC and SON were extracted and processed for nano-LC mass spectrometry (LC-MS/MS). Phosphoproteomic determinations were performed by LC-MS/MS. Results: We found many changes in the phosphoproteomes of both the CC and SON in response to 15 min of isoflurane exposure. Pathway analysis indicated that proteins undergoing phosphorylation adaptations are involved in cytoskeleton remodelling and synaptic signalling events. Importantly, changes in protein phosphorylation appeared to be brain region specific suggesting that differential phosphorylation adaptations might underlie the different neuronal activity responses to GA between the CC and SON. Conclusion: In summary, these data suggest that rapid posttranslational modifications in proteins involved in cytoskeleton remodelling and synaptic signalling events might mediate the central mechanisms mediating GA. [ABSTRACT FROM AUTHOR]