Despite the claim that blockchain will revolutionise business and redefine logistics, existing research so far is limited concerning frameworks that categorise blockchain application potentials and their implications. In particular, academic literature in transport and logistics to date has not sufficiently distinguished between blockchain adoption (‘what to adopt’) and the identification of the right business opportunity (‘where to start’). In response, this paper (1) uses Rogers’ (2003) ‘attributes of innovation framework’ to identify potential blockchain applications and (2) presents a framework explicating four transformation phases to subsequently categorise the identified areas of application according to their effects on organisational structures and processes. Using academic and practitioner literature, we classify possible applications for adoption and provide a framework to identify blockchain opportunities in the logistics industry, thereby helping managers to systematically assess where to start building organisational capabilities in order to successfully adopt and deploy blockchain-based technology.

Up to now, only limited data on long-term medical treatment in congenital hyperinsulinism (CHI) is available. Moreover, most of the drugs used in CHI are therefore not approved. We aimed to assemble more objective information on medical treatment in CHI with regard to type and duration, dosage as well as side effects. We searched MEDLINE (from 1947) and EMBASE (from 1988) using the OVID interface for relevant data to evaluate medical treatment in a large cohort of patients with CHI from different clinical centers. Randomized, controlled trials were not available. We evaluated case reports and case series. No language restrictions were made. A total number of 619 patients were medically treated and information regarding conservative treatment was available. Drugs used were diazoxide (in 84 % of patients), somatostatin analogues (16 %), calcium channel antagonists (4 %) and glucagon (1 %). Mean dose of diazoxide was 12.5 (±4.3) mg/kg ⋅ d (range 2–60 mg/kg ⋅ d), mean duration of diazoxide treatment until remission was 57 months. Side effects of diazoxide were usually not severe. The causal relation between diazoxide and severe side effects, e.g. heart failure (3.7 %) remains doubtful. Mean dose of octreotide was 14.9 (±7.5) μg/kg ⋅ d (range 2.3–50 μg/kg ⋅ d), of lanreotide 67.3 (±39.8) mg ⋅ month (range 10–120 mg ⋅ month). Mean duration of treatment with somatostatin analogues until remission was 49 months. Frequent side effects included tachyphylaxis and mild gastrointestinal symptoms. The risk of persistent growth deceleration was low (<5 %). Severe side effects are rare and a causal relation remains disputable. We conclude that long-term conservative treatment of CHI is feasible.

In an era where sustainability and efficient resource utilization are paramount, the closed-loop supply chain (CLSC) emerges as a critical approach, particularly in the context of perishable goods. The perishability of products adds a layer of complexity to supply chain management, necessitating innovative strategies for maximizing product life and minimizing waste. This comprehensive review article delves into the integration of perishable products within the framework of CLSC. The study thoroughly examines existing research to identify gaps and outline future research directions. It emphasizes the unique challenges and complexities of managing perishable goods, a crucial but often overlooked component in sustainable supply chain practices. The review highlights the balance between efficiency and sustainability, underscoring the importance of reverse logistics and circular economy principles in enhancing supply chain resilience. By synthesizing various methodologies and findings, the article presents a holistic view of the current state of perishable product management in CLSCs, offering valuable insights for academia and industry practitioners. The study not only contributes to the theoretical understanding of CLSCs, but also proposes practical approaches for their optimization, aligning with broader sustainability goals.

Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes. Expression of estrogen receptor alpha (ERα) was examined in podocytes in vitro and in vivo. Receptor localization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycin aminonucleoside (PAN, apoptosis induction), estradiol, or both in combination. Apoptotic cells were detected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM). Estradiol-induced phosphorylation of ERK1/2 and p38 MAPK was examined by Western blot. Glomeruli of ERα knock-out mice and wild-type controls were analysed by histomorphometry and immunohistochemistry. ERα was consistently expressed in human and murine podocytes. Estradiol stimulated ERα protein expression, reduced PAN-induced apoptosis in vitro by 26.5±24.6% or 56.6±5.9% (flow cytometry or Hoechst-staining, respectively; both p<0.05), and restored PAN-induced mitochondrial membrane potential depolarization. Estradiol enhanced ERK1/2 phosphorylation. In ERα knockout mice, podocyte number was reduced compared to controls (female/male: 80/86 vs. 132/135 podocytes per glomerulus, p<0.05). Podocyte volume was enhanced in ERα knockout mice (female/male: 429/371 µm³ vs. 264/223 µm³ in controls, p<0.05). Tgfβ1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage. Podocytes express ERα, whose activation leads to a significant protection against experimentally induced apoptosis. Possible underlying mechanisms include stabilization of mitochondrial membrane potential and activation of MAPK signalling. Characteristic morphological changes indicating glomerulopathy in ERα knock-out mice support the in vivo relevance of the ERα for podocyte viability and function. Thus, our findings provide a novel model for the protective influence of female gender on chronic glomerular diseases.

Objective: Genetic activation of the insulin signal-transducing kinase AKT2 causes syndromic hypoketotic hypoglycaemia without elevated insulin. Mosaic activating mutations in class 1A phospatidylinositol-3-kinase (PI3K), upstream from AKT2 in insulin signalling, are known to cause segmental overgrowth, but the metabolic consequences have not been systematically reported. We assess the metabolic phenotype of 22 patients with mosaic activating mutations affecting PI3K, thereby providing new insight into the metabolic function of this complex node in insulin signal transduction. Methods: Three patients with megalencephaly, diffuse asymmetric overgrowth, hypoketotic, hypoinsulinaemic hypoglycaemia and no AKT2 mutation underwent further genetic, clinical and metabolic investigation. Signalling in dermal fibroblasts from one patient and efficacy of the mTOR inhibitor Sirolimus on pathway activation were examined. Finally, the metabolic profile of a cohort of 19 further patients with mosaic activating mutations in PI3K was assessed. Results: In the first three patients, mosaic mutations in PIK3CA (p.Gly118Asp or p.Glu726Lys) or PIK3R2 (p.Gly373Arg) were found. In different tissue samples available from one patient, the PIK3CA p.Glu726Lys mutation was present at burdens from 24% to 42%, with the highest level in the liver. Dermal fibroblasts showed increased basal AKT phosphorylation which was potently suppressed by Sirolimus. Nineteen further patients with mosaic mutations in PIK3CA had neither clinical nor biochemical evidence of hypoglycaemia. Conclusions: Mosaic mutations activating class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver. mTOR or PI3K inhibitors offer the prospect for future therapy.