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J. Conchillo, J. Straathof, Z. Mujagic, J. Brouns, N. Bouvy, D. Keszthelyi, A. Masclee

Abstract Background and study aims There are no reliable data to predict which patients with gastroparesis (GP) would benefit the most from gastric peroral endoscopic pyloromyotomy (G-POEM). The aim of the present study was to assess whether antro-duodenal motility patterns and pyloric distensibility can predict the outcome of G-POEM in patients with decompensated GP. Patients and methods In an open-label study, patients with GP and refractory symptoms were eligible for treatment with G-POEM if treatment attempts according to a standardized stepwise protocol had failed. Baseline assessment included Gastroparesis Cardinal Symptom Index (GCSI), C13-octanoic gastric emptying breath test and high-resolution antro-duodenal manometry. Pyloric distensibility using EndoFlip measurements was assessed at baseline and 3 months after the procedure. Explorative analyses were performed on potential predictors of response using logistic regression analyses. Results Twenty-four patients with decompensated GP underwent G-POEM. At baseline, 78.3 % and 61.9 % of patients showed antral hypomotility and neuropathic motor patterns, respectively. The technical success rate was 100 % (24/24). Mean GCSI improved significantly at 3, 6, and 12 months after G-POEM (P = 0.01). Median distensibility index (DI) improved significantly as compared with baseline (7.5 [6.9;11.7] vs. 5.3[3.1;8.1], P = 0.004). A significant correlation was found between clinical response at 6 months and pyloric DI improvement (P = 0.003). No potential predictors of clinical response after G-POEM could be identified in an explorative analysis. Conclusions G-POEM improved pyloric distensibility patterns in patients with decompensated GP. Clinical response at 6 months after G-POEM was associated with pyloric distensibility improvement. However, no potential predictors of response could be identified from either antro-duodenal motility patterns or pyloric distensibility.

J. Conchillo, J. Straathof, Z. Mujagic, J. Brouns, N. Bouvy, D. Keszthelyi, A. Masclee

Abstract Background and study aims There are no reliable data to predict which patients with gastroparesis (GP) would benefit the most from gastric peroral endoscopic pyloromyotomy (G-POEM). The aim of the present study was to assess whether antro-duodenal motility patterns and pyloric distensibility can predict the outcome of G-POEM in patients with decompensated GP. Patients and methods In an open-label study, patients with GP and refractory symptoms were eligible for treatment with G-POEM if treatment attempts according to a standardized stepwise protocol had failed. Baseline assessment included Gastroparesis Cardinal Symptom Index (GCSI), C13-octanoic gastric emptying breath test and high-resolution antro-duodenal manometry. Pyloric distensibility using EndoFlip measurements was assessed at baseline and 3 months after the procedure. Explorative analyses were performed on potential predictors of response using logistic regression analyses. Results Twenty-four patients with decompensated GP underwent G-POEM. At baseline, 78.3 % and 61.9 % of patients showed antral hypomotility and neuropathic motor patterns, respectively. The technical success rate was 100 % (24/24). Mean GCSI improved significantly at 3, 6, and 12 months after G-POEM (P = 0.01). Median distensibility index (DI) improved significantly as compared with baseline (7.5 [6.9;11.7] vs. 5.3[3.1;8.1], P = 0.004). A significant correlation was found between clinical response at 6 months and pyloric DI improvement (P = 0.003). No potential predictors of clinical response after G-POEM could be identified in an explorative analysis. Conclusions G-POEM improved pyloric distensibility patterns in patients with decompensated GP. Clinical response at 6 months after G-POEM was associated with pyloric distensibility improvement. However, no potential predictors of response could be identified from either antro-duodenal motility patterns or pyloric distensibility.

V. Nagendrababu, A. Kishen, P. Murray, M. Nekoofar, J. D. de Figueiredo, E. Priya, J. Jayaraman, S. Pulikkotil et al.

Laws and ethics require that before conducting human clinical trials, a new material, device or drug may have to undergo animal testing in order to minimize the health risks to humans, unless suitable supporting grandfather data already exists. The Preferred Reporting Items for Animal Studies in Endodontology (PRIASE) 2021 guidelines were developed exclusively for the specialty of Endodontology by integrating and adapting the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines and the Clinical and Laboratory Images in Publications (CLIP) principles using a validated consensus-based methodology. The implementation of the PRIASE 2021 guidelines will reduce potential sources of bias and thus improve the quality, accuracy, reproducibility, completeness and transparency of reports describing animal studies in Endodontology. The PRIASE 2021 guidelines consist of a checklist with 11 domains and 43 individual items and a flowchart. The aim of the current document is to provide an explanation for each item in the PRIASE 2021 checklist and flowchart and is supplemented with examples from the literature in order for readers to understand their significance and to provide usage guidance. A link to the PRIASE 2021 explanation and elaboration document and PRIASE 2021 checklist and flowchart is available on the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org/priase/).

J. Cogdell, J. Jorgenson, L. Smajlović

In Cogdell et al., LMS Lecture Notes Series 459, 393–427 (2020), the authors proved an analogue of Kronecker’s limit formula associated to any divisorD which is smooth in codimension one on any smooth Kähler manifold X . In the present article, we apply the aforementioned Kronecker limit formula in the case when X is complex projective space CP for n ≥ 2 and D is a hyperplane, meaning the divisor of a linear form PD(z) for z = (Zj) ∈ CP. Our main result is an explicit evaluation of the Mahler measure of PD as a convergent series whose each term is given in terms of rational numbers, multinomial coefficients, and the L-norm of the vector of coefficients of PD.

J. Cogdell, J. Jorgenson, L. Smajlović

Abstract In [20], Rohrlich proved a modular analog of Jensen’s formula. Under certain conditions, the Rohrlich–Jensen formula expresses an integral of the log-norm $\log \Vert f \Vert $ of a ${\mathrm {PSL}}(2,{\mathbb {Z}})$ modular form f in terms of the Dedekind Delta function evaluated at the divisor of f. In [2], the authors re-interpreted the Rohrlich–Jensen formula as evaluating a regularized inner product of $\log \Vert f \Vert $ and extended the result to compute a regularized inner product of $\log \Vert f \Vert $ with what amounts to powers of the Hauptmodul of $\mathrm {PSL}(2,{\mathbb {Z}})$ . In the present article, we revisit the Rohrlich–Jensen formula and prove that in the case of any Fuchsian group of the first kind with one cusp it can be viewed as a regularized inner product of special values of two Poincaré series, one of which is the Niebur–Poincaré series and the other is the resolvent kernel of the Laplacian. The regularized inner product can be seen as a type of Maass–Selberg relation. In this form, we develop a Rohrlich–Jensen formula associated with any Fuchsian group $\Gamma $ of the first kind with one cusp by employing a type of Kronecker limit formula associated with the resolvent kernel. We present two examples of our main result: First, when $\Gamma $ is the full modular group ${\mathrm {PSL}}(2,{\mathbb {Z}})$ , thus reproving the theorems from [2]; and second when $\Gamma $ is an Atkin–Lehner group $\Gamma _{0}(N)^+$ , where explicit computations of inner products are given for certain levels N when the quotient space $\overline {\Gamma _{0}(N)^+}\backslash \mathbb {H}$ has genus zero, one, and two.

J. Cogdell, J. Jorgenson, L. Smajlović

Let X be a smooth, compact, projective Kähler variety and D be a divisor of a holomorphic form F , and assume that D is smooth up to codimension two. Let ω be a Kähler form on X and KX the corresponding heat kernel which is associated to the Laplacian that acts on the space of smooth functions on X. Using various integral transforms of KX , we will construct a meromorphic function in a complex variable s whose special value at s = 0 is the log-norm of F with respect to μ. In the case when X is the quotient of a symmetric space, then the function we construct is a generalization of the so-called elliptic Eisenstein series which has been defined and studied for finite volume Riemann surfaces.

Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression and tumor-stroma ratio (TSR) with standard clinicopathological parameters in different molecular subtypes of breast cancer.Methods: Ninety biopsy samples of primary breast cancer diagnosed at the Department of Pathology, School of Medicine, Sarajevo, were selected for this study. The molecular subtype was determined based on the immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Stromal and tumoral MMP-9 immunohistochemical expression and the TSR were determined for each tumor.Results: Tumoral MMP-9 expression correlated positively with the presence of lymphovascular invasion (p= 0.016). TSR showed significant association and correlation with tumor grade (G) (p= 0.031; p= 0.049) and tumor size (pT) (p = 0.049;p= 0.021, respectively). Stromal MMP-9 expression correlated with histologic type, histologic grade of tumor, and lymphocytic inflammatory infiltrate (p= 0.021;p= 0.047, p= 0.038, respectively). A higher percentage of stromal MMP-9 expression correlated with the strongest lymphocytic response (p = 0.007). Significant correlation was observed between molecular subtypes and histologic grade of the tumor (p= 0.032).Conclusion: Our results, to some extent, confirm the significance of the tumor microenvironment in breast cancer, especially when it is about stromal MMP-9 expression. Although we observed significant association, without linear correlation, we found no significant correlation between molecular subtypes of breast cancer and MMP-9 expression.

A. Crnogorac, S. Panno, A. Mandić, Mladen Gašpar, A. Caruso, E. Noris, S. Davino, S. Matić

The sanitary status of grapevines has not yet been considered sufficiently in vineyards throughout Bosnia and Herzegovina (BiH). An extensive survey of five major grapevine viruses in the country was carried out in 2019. A total of 630 samples from the two dominant autochthonous cultivars, named Žilavka and Blatina, were tested by DAS-ELISA for the presence of grapevine leafroll-associated viruses (GLRaV-1 and 3), grapevine fleck virus (GFkV), grapevine fanleaf virus (GFLV) and Arabis mosaic virus (ArMV). Eighty-eight % of the samples were positive for at least one virus, and all five viruses were detected, thought with different incidence, i.e. GLRaV-3 (84%), GFLV (43%), GLRaV-1 (14%), GFkV (10%) and ArMV (0.2%). The majority of infected plants (about 75%) were asymptomatic. Specific virus symptoms were observed in the remaining infected plants, together with the reported GLRaV vectors, Planococcus ficus and Parthenolecanium corni, while nematodes of the Xiphinema genus were not found in the GFLV- or ArMV-infected vineyards. The GLRaV-3 CP phylogenetic analyses showed 75–100% nucleotide identity between the BiH and reference isolates, and the BiH isolates clustered into the major group. The dNS/dS ratio indicated a negative selection of the virus population, and the lack of geographical structuring within the population was observed. In addition, putative GLRaV-3 recombinants with breakpoints in the 5’ of the CP gene were detected, while no recombinant strains were identified for the other four viruses. The obtained results indicate a deteriorated sanitary status of the cultivated grapevines, the prevalence and intraspecies genetic diversity of GLRaV-3 throughout the country. The establishment of certified grapevine material and adequate virus vector control is therefore of primary importance to prevent further spread of these viruses. This study presents the results of the first molecular characterisation of grapevine viruses in Bosnia and Herzegovina.

G. Tomson, S. Causevic, O. Ottersen, Stefan Swartling Peterson, S. Rashid, Rhoda K. Wanyenze, A. Yamin

Göran Tomson and colleagues argue that our ability to control pandemics requires global action to counter inequalities from demographic, environmental, technological, and other megatrends

M. Buck, Enzo Z. Poirier, A. Cardoso, Bruno Frederico, Johnathan Canton, S. Barrell, R. Beale, Richard Byrne et al.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated procedure for high-throughput SARS-CoV-2 detection by RT-LAMP that is robust, reliable, repeatable, specific, and inexpensive.

Sabrina E. Wang, A. Hodge, S. G. Dashti, S. Dixon-Suen, H. Mitchell, R. Thomas, E. Williamson, E. Makalic et al.

Abstract Objective: To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD). Design: Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined. Setting: Melbourne, Australia. Participants: A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994. Results: For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores. Conclusions: Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.

A. Macken, A. Prkić, K. Koenraadt, I. van Oost, A. Spekenbrink-Spooren, B. The, D. Eygendaal

Background This study aims to use the Dutch Arthroplasty Register data to report an overview of the contemporary indications and implant designs, and report the short-term survival of radial head arthroplasty. Methods From the Dutch Arthroplasty Register, data on patient demographics, surgery and revision were extracted for radial head arthroplasties performed from January 2014 to December 2019. Implant survival was calculated using the Kaplan–Meier method. Results Two hundred fifty-eight arthroplasties were included with a median follow-up of 2.2 years. The most common indication was a fracture of the radial head (178, 69%). One hundred thirty-nine (68%) of the prostheses were of bipolar design, and the most commonly used implant type was the Radial Head System (Tornier; 134, 51%). Of the 258 included radial head arthroplasties, 16 were revised at a median of six months after surgery. Reason for revision was predominantly aseptic loosening (9). The overall implant survival was 95.8% after one year, 90.5% after three years and 89.5% after five years. Discussion For radial head arthroplasties, acute trauma is the most common indication and Radial Head System the most commonly used implant. The implant survival is 89.5% after five years.

J. Mulec, Andreea Oarga-Mulec, L. Holko, L. Pasic, A. Kopitar, T. Eleršek, A. Mihevc

Paradana is one of the biggest ice caves in Slovenia, with an estimated ice volume of 8,000 m3. Reflecting climatological conditions, the cave ice undergoes repeated freeze-thaw cycles and regular yearly deposition of fresh ice. Three distinct ice block samples, collected from the frozen lake in May 2016, were analysed to obtain data on ice physicochemical properties and the composition of associated microbiota. Isotopic composition of the ice samples (18O, 2H) and a local meteoric water line (LMWL) constructed for monthly precipitation at Postojna were used to estimate the isotopic composition of the water that formed the ice, which had high values of deuterium excess and low concentrations of chloride, sulphate and nitrate. The values of total organic carbon (1.93–3.95 mg/l) within the ice blocks fall within the range of those measured in karst streams. Total cell count in the ice was high and the proportion of cell viability increased along the depth gradient and ranged from 4.67 × 104 to 1.52 × 105 cells/ml and from 51.0 to 85.4%, respectively. Proteobacteria represented the core of the cave-ice microbiome (55.9–79.1%), and probably play an essential role in this ecosystem. Actinobacteria was the second most abundant phylum (12.0–31.4%), followed in abundance by Bacteroidetes (2.8–4.3%). Ice phylotypes recorded amounted to 442 genera, but only 43 genera had abundances greater than 0.5%. Most abundant were Pseudomonas, a well-known ice dweller, and Lysobacter, which previously was not reported in this context. Finally, two xanthophytes, Chloridella glacialis and Ellipsoidion perminimum, known from polar environments, were cultured from the ice. This indicates that the abundance and ecological role of phototrophs in such environments might be greater than previously deduced.

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