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Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations.Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital.Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/ .Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child’s sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. Results: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child’s future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent–infant bonding, and reported variable impact on their feelings of guilt. Conclusion: Parents reported that GS during the neonatal period was useful because it provided a “backbone” for their child’s care. Parents did not consistently endorse negative impacts like interference with parent–infant bonding.

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior–superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

Physical science depends on historical records as well as new ideas, results, and opportunities. In this increasingly digital era, in which much of modern day life is technology-driven, a significant amount of scientific data remains in forms that are inaccessible to current methods. Moreover, the creation and subsequent accessing of high quality reusable data continues to present challenges. As part of the pilot phase of the Physical Sciences Data Infrastructure (PSDI) Initiative we investigated the current landscape of digitisation in 2022, aiming to produce an outline of what the physical sciences community requires from a Digital Research Environment (DRE). Evidence suggests that while scientists are digitising diverse portions of their work, some research still remains lost in paper lab books, and many barriers (hardware, software and people) persist for the effective management of scientific data. Our studies build on previous research and include an informal survey of what the UK Physical Sciences community considered to be the key requirements for capturing, sharing, and accessing data. The paper ends by outlining future prospects for PSDI and provides some concrete actions for different stakeholders in the community.

Biodiversity is crucial for supporting ecosystem functioning, yet some species play a disproportionate role in maintaining complex ecological processes. Ecosystem engineers are species that directly influence ecosystems by modifying biophysical environments, creating novel habitats, altering biogeochemical cycles, increasing biodiversity and/or modulating ecological processes. Although these species may substantially influence ecosystem functioning, their role is often overlooked and difficult to quantify. Understanding the status, dynamics and trends of ecosystem engineers is essential for mitigating biodiversity loss and maintaining healthy ecosystems. This review reveals the common but underappreciated roles that ecosystem engineers play in ecosystem functioning across many different taxa, biomes and ecological processes. We first synthesise how knowledge of ecosystem engineering improves our understanding of species interactions and the ecological processes underlying both ecosystem functioning and BEF relationships. We provide a conceptual model for addressing the effects of ecosystem engineers in BEF research and ecological dynamics. We provide a ‘how to’ analytical framework for monitoring and quantifying changes in ecosystem engineers and their effects on ecosystem functioning. This framework includes (i) what variables to measure, how and at which scale; (ii) experiments involving species exclusion or removal, introduction and comparative designs when experimental manipulation is not feasible and (iii) statistical, data-driven and theory-driven models. We discuss how to leverage ecosystem engineering in the context of current global change and ecosystem restoration efforts. Including ecosystem engineers in conservation and restoration programs, when implemented in the appropriate context and supported by an understanding of ecological mechanisms and processes, may be crucial for sustaining biological diversity and functional ecosystems.

The purpose of this retrospective pilot study was to examine the short-term effect of simultaneous Ahmed Glaucoma Valve implantation and cyclophotocoagulation on postoperative outcomes in patients with neovascular glaucoma.Patient charts were selected for inclusion in this study if they carried a diagnosis of neovascular glaucoma and underwent Ahmed glaucoma valve implantation only, Ahmed glaucoma valve implantation with cyclophotocoagulation, or cyclophotocoagulation only. A total of 55 eyes of 54 patients were selected for data collection and analysis. Main outcome measures included 1-, 3-, and 6-month intraocular pressure and occurrence of the hypertensive phase. Other outcomes included visual acuity, surgical complication rate, and a number of 6-month postoperative ophthalmic medications.A significantly lower intraocular pressure was seen in the group that received Ahmed glaucoma valve implantation + cyclophotocoagulation compared to the Ahmed glaucoma valve-only group at 3 and 6 months (Simultaneous Ahmed glaucoma valve implantation and cyclophotocoagulation significantly lowered intraocular pressure at 3 and 6 months compared to Ahmed glaucoma valve implantation alone in patients with neovascular glaucoma.Neovascular glaucoma is difficult to manage medically and surgically. When surgery is performed, intraocular pressure often remains elevated postoperatively despite aggressive medical management. This study examines a novel method to lower intraocular pressure after Ahmed glaucoma valve implantation in patients with neovascular glaucoma.Ford RL, Knight ORJ, Klifto MR

PURPOSE: SouthSeq is a translational research study that performed genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern US that are historically under-represented in genomic medicine research. METHODS: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. RESULTS: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants and 14% harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. CONCLUSION: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

Engaging patients in the research process helps to ensure researchers ask meaningful questions and generate useful evidence to inform healthcare decisions. In 2015, the Veterans Health Administration (VA) Health Services Research & Development (HSR&D) service convened a Veteran engagement workgroup, comprised of researchers, clinicians, and Veterans, to identify ways to integrate Veteran engagement into HSR&D. A subgroup was designated to explore the utility of health experiences research (research focused on enhancing understanding of people’s experiences with healthcare and illnesses) as a mechanism to complement and broaden traditional engagement mechanisms. The subgroup recommended the VA adopt the Database of Individual Patient Experiences (DIPEx) methodology for conducting and disseminating health experiences research (HER). In this paper, we describe (1) the key components of the DIPEx approach, (2) how these components complement and broaden current methods of Veteran engagement, (3) an update on VA activities using the DIPEx approach, and (4) a roadmap for future VA HER activities.

IR reduced xenograft growth in intact mice without androgen modulation. Xenograft tumors of LAPC4 (A) and LNCaP (B) cells established in intact nude mice were exposed to sham (control) or 8Gy ionizing radiation (IR). Tumor size was longitudinally determined by caliper measurements. Graph shows relative tumor volumes normalized to the tumor size at the time of radiation.

Purpose: The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR).Experimental Design: Androgen-induced DNA damage was assessed by comet assays and γH2A.X foci formation. Effects of androgen stimulation and radiation were determined in vitro and in vivo with xenograft models.Results: We document that androgen treatment of androgen-deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. In vitro models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, in vivo studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice.Conclusions: These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. Clin Cancer Res; 22(13); 3310–9. ©2016 AACR.See related commentary by Chua and Bristow, p. 3124

Clonogenic survival of PC3 cells following IR and DHT treatments. Clonogenic survival fraction is shown for AR negative PC3 cells exposed to vehicle control, 100 nM DHT, 4 Gy of IR or the combination of both. NS, not significant.

DNA repair genes following androgen stimulation. Androgen-deprived LNCaP cells were exposed to vehicle or 100nM DHT for the indicated times and mRNA of classical AR-regulated genes (A) or DNA repair-related genes (B) were measured using qRT-PCR. mRNA levels are expressed relative to GAPDH expression and normalized to levels in androgen-deprived conditions.

Formation of androgen induced DSB requires AR and TOP2B.

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There is evidence that vineyard yeast communities are regionally differentiated, but the extent to which this contributes to wine regional distinctiveness is not yet clear. This study represents the first experimental test of the hypothesis that mixed yeast communities—comprising multiple, region-specific, isolates, and species—contribute to regional wine attributes. Yeast isolates were sourced from uninoculated Pinot Noir fermentations from 17 vineyards across Martinborough, Marlborough, and Central Otago in New Zealand. New methodologies for preparing representative, mixed species inoculum from these significantly differentiated regional yeast communities in a controlled, replicable manner were developed and used to inoculate Pinot Noir ferments. A total of 28 yeast-derived aroma compounds were measured in the resulting wines via headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. Yeast community region of origin had a significant impact on wine aroma, explaining ∼10% of the observed variation, which is in line with previous reports of the effects of region-specific Saccharomyces cerevisiae isolates on Sauvignon Blanc ferments. This study shows that regionally distinct, mixed yeast communities can modulate wine aroma compounds in a regionally distinct manner and are in line with the hypothesis that there is a microbial component to regional distinctiveness, or terroir, for New Zealand Pinot Noir.

The purpose of this study was to report a case of corneal transparency for 7 months after the formation and persistence of a Descemet fluid cleft.We report the case of a 64-year-old woman undergoing anterior chamber reformation 2 months after Baerveldt implantation of the right eye. During the procedure, the ophthalmic viscoelastic was inadvertently injected into the posterior stroma, nearly isolating the corneal endothelial cell layer, and creating a Descemet fluid cleft filled with viscoelastic. The patient was managed conservatively and monitored near monthly for corneal decompensation.The cornea remained centrally clear for 207 days after the initial anterior chamber reformation until the collapse of the viscoelastic cleft. When the cleft completely collapsed, the cornea became diffusely edematous, and the patient underwent cataract removal and intraocular lens placement without need for Descemet stripping endothelial keratoplasty to maintain vision. During these 7 months, the patient's best-corrected visual acuity remained stable at 20/25 +2 or better. Intraocular pressure was also stable, averaging 18.2 mm Hg.We hypothesize that corneal transparency can be maintained in the absence of endothelial cell function provided that aqueous humor cannot reach the cornea and disrupt the arrangement of the interfibrillar space.