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Artificial Intelligence (AI) tools are being developed to assist with increasingly complex diagnostic tasks in medicine. This produces epistemic disruption in diagnostic processes, even in the absence of AI itself, through the datafication and digitalization encouraged by the promissory discourses around AI. In this study of the digitization of an academic pathology department, we mobilize Barad's agential realist framework to examine these epistemic disruptions. Narratives and expectations around AI-assisted diagnostics—which are inextricable from material changes—enact specific types of organizational change, and produce epistemic objects that facilitate to the emergence of some epistemic practices and subjects, but hinder others. Agential realism allows us to simultaneously study epistemic, ethical, and ontological changes enacted through digitization efforts, while keeping a close eye on the attendant organizational changes. Based on ethnographic analysis of pathologists' changing work processes, we identify three different types of uncertainty produced by digitization: sensorial, intra-active, and fauxtomated uncertainty. Sensorial and intra-active uncertainty stem from the ontological otherness of digital objects, materialized in their affordances, and result in digital slides' partial illegibility. Fauxtomated uncertainty stems from the quasi-automated digital slide-making, which complicates the question of responsibility for epistemic objects and related knowledge by marginalizing the human. [ABSTRACT FROM AUTHOR]

The digitalization of healthcare work has gained center stage in academic debates spanning disciplines as diverse as medicine, sociology and STS. The different analytical interests and methodological traditions of these three strains of scholarship have, however, resulted in quite diverging approaches to this issue. Points of interest have ranged from the (disattended) promise of increased efficiency of healthcare work, to dynamics of task delegation, (re-)professionalization and (re-)distribution of invisible work, to the disruption of informal organization. Instead of studying these dynamics in practice, in this paper we foreground the potentiality for theory-making inherent in the systematic cross-contamination of different theoretical and disciplinary perspectives. We perform a Critical Interpretive Synthesis (CIS) centering the ways the digitalization of healthcare work has been investigated in recent STS, sociological and medical literature. To open up assumptions and insights intrinsic to each body of literature for scholars and practitioners in other fields, we propose here a metaphor-based variation on CIS approaches. We probe, in turn, what slime molds can teach us about STS's focus on interconnections and materiality, how we can better understand sociological analyses of invisible work exploring them through theatrical performances, and which lessons river engineering offers concerning medical scholarship's discussion of efficiency and proper healthcare work. Thinking through these metaphors, we conceptualize the digitalization of healthcare work as a phenomenon spanning, at once, the directionality of technological innovation trajectories and the open-endedness of situated changes in work practices. Based on our analysis, we propose focusing on technological scripts, and various forms of invisible work and informal organization as entry points into the study of the tension between directionality and open-endedness in the context of the digitalization of healthcare work. • Metaphors are a productive way of synthetizing multidisciplinary literature. • Slime mold articulates insights inherent in STS's focus on networks and materiality. • Scripts and stagehands describe sociology's focus on hierarchy and invisible work. • River engineering alerts us to the tradeoffs of medicine's concept of workflow. • Directionality and open-endedness coexist in the digitalization of healthcare work. [ABSTRACT FROM AUTHOR]

Despite the availability of standard therapy (vitamin D sterols and phosphate binders) for the treatment of secondary hyperparathyroidism (SHPT) in hemodialyzed (HD) patients, a significant percentage of patients still fail to achieve targets recommended by the Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation for parathyroid hormone (PTH), calcium, and phosphorus. The calcimimetic cinacalcet (CN) has been shown to be an effective treatment for SHPT, significantly reducing serum PTH while simultaneously lowering calcium, phosphorus, and calcium-phosphorus product levels, thus increasing the proportion of patients achieving the K/DOQI targets for bone mineral parameters. The aim of this study was to evaluate if early treatment with CN had beneficial effects in HD patients with mild-to-moderate SHPT in whom conventional treatments had failed to achieve NKF-K/DOQI targets for PTH, serum-corrected calcium, and phosphorus while minimizing the risk of paradoxical hypercalcemia and/or hyperphosphatemia. Clinical practice data were collected monthly, starting from 6 months prior to, and up to 36 months after, the start of CN therapy. CN was started at a dose of 30 mg daily or every other day, and titrated thereafter to achieve intact PTH (iPTH) <300 pg/mL. The dose of concomitant vitamin D and phosphate binders were also adjusted in order to achieve K/DOQI targets. Data from 32 patients were collected, 28 of whom had been treated with CN for at least 36 months at the time of data analysis. At baseline, patients had serum iPTH >300 pg/mL (570 ± 295 pg/mL) and/or serum-corrected calcium >9.5 mg/dL. CN induced significant decreases in iPTH, calcium, and calcium-phosphorus product with respect to baseline levels. The percentage of patients within K/DOQI target levels at baseline, 12, 24, and 36 months was 0, 81.2, 83.3, and 86.2% for iPTH; 34.4, 65.6, 86.6, and 89.6% for serum-corrected calcium; 40.6, 56.2, 69.6, and 72.4% for phosphorus; and 37.5, 62.5, 80, and 82.7% for calcium-phosphorus product. The mean dose of CN at the end of the observation period was 38 mg/day. The mean dose of concomitant medication (calcitriol, Al-containing phosphate binders, and sevelamer) decreased from baseline to 36 months. Early treatment with CN in HD patients with SHPT increases the proportion of patients achieving and maintaining K/DOQI targets with a low dose of CN (38 mg/day). These results suggest that the metabolic control obtained with low-dose CN administered early in the course of SHPT can be maintained or increased over time. [ABSTRACT FROM AUTHOR]

Abstract: We have demonstrated for the first time that d-glutamine (d-Gln) and d-glutamic acid (d-Glu) can be efficiently obtained in high ee (97% and 90%, respectively) by enzymatic kinetic resolution of d,l-Gln and d,l-Glu. This was achieved by enantioselective conversion of the l-enantiomers to their N-phenylacetyl derivatives in aqueous solution, using a mutant of penicillin-G acylase (PGA) from E. coli and phenylacetic acid methylester as the acyl donor. Kinetic modeling studies suggest that the high ee values obtained are both due to a strong enantiopreference for the l-amino acid in the deacylation step of the covalent enzyme intermediate, as well as to completeness of conversion that is transiently obtained as a result of the distinct preference of the mutant PGA for phenylacetic acid methylester over the N-phenylacetyl-l-amino acid product. For the other amino acids tested (Asn, Asp, and Ser), the highest ee values that were obtained for the remaining d-enantiomer are moderate (50–80%) because of lower enantioselectivity in the enzyme deacylation step and due to less complete conversion of the l-amino acid caused by competition for the active site between the acyl donor and the N-phenylacetyl-l-amino acid that is produced. The results demonstrate that the mutated PGA has great potential for the production of optically active d-amino acids by kinetic resolution. [Copyright &y& Elsevier]

Objective: No-visitor policies adopted to prevent coronavirus disease-19 (COVID-19) spread in hospital wards have deeply impacted communication with patients and their relatives. Whereas in pre-COVID-19 era family-clinician meetings were held in person, during the pandemic interactions often took place over the phone, frequently causing feelings of uncertainty and distress to the close ones at home. The goal of this study was to assess and improve the effectiveness of structured telephone-based communication with hospitalized onco-hematological patients' relatives in COVID-19 era. Methods: After no-visitor policy was adopted in the Onco-Hematological Unit of Modena, inpatients' relatives were contacted daily for clinical updates. After discharge, a telephone satisfaction survey was administered to all contact people of patients consecutive admitted between December 2020 and January 2021 (n = 97). Mean score of response and potential statistically significative differences depending on respondents' characteristics were assessed. Results: Most relatives were satisfied with the communication received with a mean total score of 4.69 on a 5-point Likert scale (standard deviation: 0.60). Results showed high satisfaction rate with both the informative (mean ± SD: 4.66 ± 0.64) and emotional (mean ± SD: 4.66 ± 0.58) content, with no significant difference depending on respondents' demographic characteristics (p > 0.05). Conclusion: A structured telephone-based communication may be a reasonable substitute for face-to-face meetings; especially if regular in time, conducted by the same doctor and integrated with video calls. Our findings might assist health workers in implementing measures to minimize the psychological effects of no-visitor policies during hospitalization. Clinical updates delivery through structured phone calls and video calls could become an opportunity also in post-COVID era. [ABSTRACT FROM AUTHOR]

Histone deacetylase inhibitors represent a family of targeted anticancer compounds that are widely used against hematological malignancies. So far little is known about their effects on normal myelopoiesis. Therefore, in order to investigate the effect of histone deacetylase inhibitors on the myeloid commitment of hematopoietic stem/progenitor cells, we treated CD34+ cells with valproic acid (VPA). Our results demonstrate that VPA treatment induces H4 histone acetylation and hampers cell cycle progression in CD34+ cells sustaining high levels of CD34 protein expression. In addition, our data show that VPA treatment promotes erythrocyte and megakaryocyte differentiation. In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor–independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites. Finally, we show that GFI1B inhibition impairs erythroid and megakaryocyte differentiation induced by VPA, while MLLT3 silencing inhibits megakaryocyte commitment only. As a whole, our data suggest that VPA sustains the expression of stemness-related markers in hematopoietic stem/progenitor cells and is able to interfere with hematopoietic lineage commitment by enhancing erythrocyte and megakaryocyte differentiation and by inhibiting the granulocyte and mono-macrophage maturation. [Copyright &y& Elsevier]