bluuebunny/crossref_metadata_2025 huggingface dataset:
Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis
Authors: Baum Joanna , Zickler Daniel , Bolbrinker Juliane , Richter Rolf , Braicu Elena Ioana , Grabowski Jacek , Sehouli Jalid
Published: March 2023

Purpose

For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis.

Methods

Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state.

Results

Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUCss was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CLss/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples.

Conclusion

A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted.
How well do high-resolution Global Climate Models (GCMs) simulate tropical cyclones in the Bay of Bengal?
Authors: Akhter Shammi , Holloway Christopher E. , Hodges Kevin , Vanniere Benoit
Published: March 2023

Using six HighResMIP multi-ensemble GCMs (both the atmosphere-only and coupled versions) at 25 km resolution, the Tropical Cyclone (TC) activity over the Bay of Bengal (BoB) is examined in the present (1950–2014) climate. We use the Genesis Potential Index (GPI) to study the large-scale environmental conditions associated with the TC frequency in the models. Although the models struggle to reproduce the observed frequency and intensity of TCs, most models can capture the bimodal characteristics of the seasonal cycle of cyclones over the BoB (with fewer TCs during the pre-monsoon [April–May] than the post-monsoon [October–November] season). We find that GPI can capture the seasonal variation of the TC frequency over the BoB in both the observations and models. After calibrating the maximum sustained windspeeds in the models with IBTrACS, we find that like the observations the proportion of strong cyclones is also higher in the pre-monsoon than the post-monsoon. However, the inter-seasonal contrast of the proportion of strong cyclones between the pre-monsoon and post-monsoon seasons is reduced in almost all the models compared to the observations. The windshear term in GPI contributes the most to the model biases in all models during the post-monsoon season. This bias is caused by weakening of upper-level (200 hPa) easterlies in analysed models. During the pre-monsoon season, the environmental term in GPI dominating the model biases varies from model to model. When comparing the atmosphere-only and coupled versions of the models, a reduction of 0.5 °C in the sea surface temperature (SST) and a lowering of TC frequency occur in almost all the coupled models compared to their atmosphere-only counterparts.
Impacts of a weakened AMOC on precipitation over the Euro-Atlantic region in the EC-Earth3 climate model
Authors: Bellomo Katinka , Meccia Virna L. , D’Agostino Roberta , Fabiano Federico , Larson Sarah M. , von Hardenberg Jost , Corti Susanna
Published: March 2023

Given paleoclimatic evidence that the Atlantic Meridional Overturning Circulation (AMOC) may affect the global climate system, we conduct model experiments with EC-Earth3, a state-of-the-art GCM, to specifically investigate, for the first time, mechanisms of precipitation change over the Euro-Atlantic sector induced by a weakened AMOC. We artificially weaken the strength of the AMOC in the model through the release of a freshwater anomaly into the Northern Hemisphere high latitude ocean, thereby obtaining a ~ 57% weaker AMOC with respect to its preindustrial strength for 60 model years. Similar to prior studies, we find that Northern Hemisphere precipitation decreases in response to a weakened AMOC. However, we also find that the frequency of wet days increases in some regions. By computing the atmospheric moisture budget, we find that intensified but drier storms cause less precipitation over land. Nevertheless, changes in the jet stream tend to enhance precipitation over northwestern Europe. We further investigate the association of precipitation anomalies with large-scale atmospheric circulations by computing weather regimes through clustering of geopotential height daily anomalies. We find an increase in the frequency of the positive phase of the North Atlantic Oscillation (NAO+), which is associated with an increase in the occurrence of wet days over northern Europe and drier conditions over southern Europe. Since a ~ 57% reduction in the AMOC strength is within the inter-model range of projected AMOC declines by the end of the twenty-first century, our results have implications for understanding the role of AMOC in future hydrological changes.
Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure
Authors: Oeing Christian U. , Pepin Mark E. , Saul Kerstin B. , Agircan Ayça Seyhan , Assenov Yassen , Merkel Tobias S. , Sedaghat-Hamedani Farbod , Weis Tanja , Meder Benjamin , Guan Kaomei , Plass Christoph , Weichenhan Dieter , Siede Dominik , Backs Johannes
Published: March 2023

Precision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium. Neonatal rat ventricular myocytes (NRVMs) and single-origin human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and were treated with blood plasma samples from patients with dilated cardiomyopathy (DCM) and donor subjects lacking history of cardiovascular disease. Following plasma treatments, NRVMs and hiPSC-CMs underwent significant hypertrophy relative to non-failing controls, as determined via automated high-content screening. Array-based DNA methylation analysis of plasma-treated hiPSC-CMs and cardiac biopsies uncovered robust, and conserved, alterations in cardiac DNA methylation, from which 100 sites were validated using an independent cohort. Among the CpG sites identified, hypo-methylation of the ATG promoter was identified as a diagnostic marker of HF, wherein cg03800765 methylation (AUC = 0.986, P < 0.0001) was found to out-perform circulating NT-proBNP levels in differentiating heart failure. Taken together, these findings support a novel approach of indirect epigenetic testing in human HF.
Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia
Authors: Rosenbrock Holger , Desch Michael , Wunderlich Glen
Published: March 2023

Schizophrenia is a psychiatric disorder characterised by symptoms in three domains: positive (e.g. delusions, hallucinations), negative (e.g. social withdrawal, lack of motivation) and cognitive (e.g. working memory and executive function impairment). Cognitive impairment associated with schizophrenia (CIAS) is a major burden for patients and negatively impacts many aspects of a patient’s life. Antipsychotics are the standard-of-care treatment for schizophrenia but only address positive symptoms. So far there are no approved pharmacotherapies for the treatment of CIAS. Iclepertin (BI 425809) is a novel, potent and selective glycine transporter 1 (GlyT1) inhibitor, under development by Boehringer Ingelheim for the treatment of CIAS. Phase I studies have shown it to be safe and well tolerated in healthy volunteers, and central target engagement (inhibition of GlyT1) was achieved in a dose-dependent manner from 5 to 50 mg in healthy volunteers. A Phase II study has demonstrated that iclepertin is safe and well tolerated in patients with schizophrenia and improves cognition at doses of 10 mg and 25 mg. Phase III studies are ongoing to confirm these initial positive safety and efficacy findings with the 10 mg dose, and if successful, iclepertin could become the first approved pharmacotherapy used to treat CIAS.
Baseline brain imaging signs in patients with ischaemic stroke by the presence of atrial fibrillation: the ENCHANTED trial
Authors: Wang Xia , You Shoujiang , Zhou Zien , Delcourt Candice , Wardlaw Joanna , Mair Grant , Robinson Thompson , Chen Xiaoying , Yoshimura Sohei , Torii-Yoshimura Takako , Carcel Cheryl , Malavera Alejandra , Anderson Craig , Lindley Richard I.
Published: March 2023

Background

We aimed to assess the association of atrial fibrillation (AF) on outcomes in a post hoc analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) and how this association is modified by baseline imaging features.

Methods

Inverse probability of treatment weight was used to remove baseline imbalances between those with and without AF. The primary outcome was the modified Rankin Scale (mRS) scores at 90 days. Secondary outcomes were symptomatic intracerebral haemorrhage (sICH), early neurological deterioration or death within 24 h, and death at 90 days. The logistic regression model was used to determine the associations.

Results

Of the 3285 patients included in this analysis, 636 (19%) had AF at baseline. Compared with non-AF, AF was not significantly associated with an unfavourable shift of mRS (odds ratio 1.09; 95% confidence interval, 0.96–1.24), but with sICH (2.82; 1.78-4.48; IST-3 criteria), early neurological deterioration or death within 24 h (1.31; 1.01-1.70), and death (1.42; 1.12-1.79). Among patients with acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions), AF was associated with the increased risk of all the poor outcomes (all P < 0.04 for interaction).

Conclusions

We found AF increased risk of sICH, early neurological deterioration or death and death, but not unfavourable functional recovery at day 90 after thrombolysis in patients with AIS. The presence of acute ischaemic brain imaging signs at stroke presentation could be used to improve risk stratification in the presence of AF.

Trial registration

The trial is registered at ClinicalTrials.gov (NCT01422616).
Remote effects of a 7-week combined stretching and foam rolling training intervention of the plantar foot sole on the function and structure of the triceps surae
Authors: Konrad Andreas , Reiner Marina Maren , Gabriel Anna , Warneke Konstantin , Nakamura Masatoshi , Tilp Markus
Published: March 2023

It is known that a single bout of foam rolling (FR) or stretching can induce changes in range of motion (ROM) and performance in non-directly adjoining areas of the dorsal chain (i.e., remote effects). However, to date, it is not known if such effects exist following long-term interventions. Thus, the purpose of this study was to investigate the remote effects of a 7-week combined stretching and FR training intervention of the plantar foot sole. Thirty-eight recreational athletes were randomly assigned to either an intervention (n = 20) or control (n = 18) group. The intervention group performed stretching and FR exercises of the plantar foot sole for 7 weeks. Before and after the intervention, the dorsiflexion ankle ROM, passive resistive torque at maximum angle (PRTmax) and at a fixed angle, as well as maximum voluntary isometric contraction (MVIC) torque, were measured with a dynamometer. Gastrocnemius medialis and lateralis stiffness was assessed with shear wave elastography. The results showed no interaction effect for any of the parameters. There was a time effect indicating an increase in MVIC and PRTmax, which was more pronounced in the intervention group (+ 7.4 (95% CI 2.5–12.4),  + 4.5 (95% CI − 0.2–9.2)) than the control group (+ 3.6 (95% CI − 1.4–8.6),  + 4.0 (95% CI − 2.2 to 10.2)). The results indicate no or minor remote effects of combined stretching and FR of the foot sole in the ankle joint. Potential non-significant changes in ROM were accompanied with an increase in stretch tolerance, but not with changes in muscle structure.
Tutte Embeddings of Tetrahedral Meshes
Authors: Alexa Marc
Published: March 2023

Tutte’s embedding theorem states that every 3-connected graph without a $$K_5$$

K
5

- or $$K_{3,3}$$

K

3
,
3

-minor (i.e., a planar graph) is embedded in the plane if the outer face is in convex position and the interior vertices are convex combinations of their neighbors. We show that this result extends to simply connected tetrahedral meshes in a natural way: for the tetrahedral mesh to be embedded if the outer polyhedron is in convex position and the interior vertices are convex combination of their neighbors it is sufficient (but not necessary) that the graph of the tetrahedral mesh contains no $$K_6$$

K
6

and no $$K_{3,3,1}$$

K

3
,
3
,
1

, and all triangles incident on three boundary vertices are boundary triangles.
Locking treatment of penalty-based gradient-enhanced damage formulation for failure of compressible and nearly incompressible hyperelastic materials
Authors: Valverde-González A. , Reinoso J. , Dortdivanlioglu B. , Paggi M.
Published: March 2023

Soft materials are of major interest for biomechanics applications due to their high deformability and susceptibility to experience damage events under different loading scenarios. The present study is concerned with modelling damage evolution processes in these nonlinear materials whose structural responses are prone to locking when low-order kinematic interpolation is employed in the context of nonlinear Finite Element schemes. For this reason, a pair of gradient-enhanced continuum damage schemes are proposed with the aim of tackling mechanical failure problems in applications that exhibit shear and volumetric locking. In particular, we present the consistent formulation and the assessment of the corresponding performance of (i) a mixed displacement-enhanced assumed strain employing a total Lagrangian formulation, and (ii) a three-field mixed displacement-pressure-Jacobian formulation. The novel and formulations are consistently derived and numerically implemented, providing a satisfactory agreement with respect to built-in elements handling the treatment of shear and volumetric locking, respectively, in conjunction to the modelling damage phenomena via the use of a penalty-based gradient-enhanced formulation. This performance is examined via several numerical applications. Furthermore, the final example justifies the need for a formulation combining both mixed FE approaches to simulate problems encompassing both locking issues (shear and volumetric locking), which can be performed using a combination of the and herein proposed.
The decrease in diurnal oxygen production in Elodea under the influence of high geomagnetic variability: the role of light, temperature and atmospheric pressure
Authors: Davies Elizabeth
Published: March 2023

Epidemiological studies have indicated adverse effects of geomagnetic disturbance on human health, including increased mortality. There is evidence from plant and animal studies that help to elucidate this interaction. This study tests the hypothesis that geomagnetic disturbance affects living systems, by modifying the metabolic process of photosynthesis, in the natural environment.

Continuous 24-h measurements of dissolved oxygen in flasks containing Holtfreiter’s solution and strands of healthy Elodea were recorded from May 1996, until September 1998, in an electromagnetically quiet, purpose built, garden shed environment, without mains electricity. Sensormeter recordings of oxygen, light, temperature and air pressure were uploaded weekly to a PC. The hourly total geomagnetic field measurements were obtained from the nearest observatory.

Significant decrease in oxygen (diurnal volume of oxygen divided by plant mass and diurnal light), (O/WL), was found on days of high geomagnetic field variability throughout 11 recorded months of the year 1997. This result was independent of temperature and atmospheric pressure. No significant decrease in O/WL during high geomagnetic variability was found for the 7 months recorded in 1996. The 1996 and 1997 data both showed a significant decrease in the diurnal time lag between peak light and peak oxygen for diurnal high geomagnetic variability compared with low geomagnetic variability. Cross correlation analysis for 1997 and 1998 data showed a decrease in positive correlation of oxygen with light in high geomagnetic variability, compared with low geomagnetic variability, and increased positive correlation with the geomagnetic field instead. These experiments support a hypothesis of high geomagnetic field variability as a weak zeitgeber, and a metabolic depressant for photosynthetic oxygen production in plants.
Design of hairpin windings considering the transient potential distribution
Authors: Dittmann Jochen , England Marc , Ponick Bernd
Published: March 2023

With the increasing use of novel semiconductor technologies such as SiC and GaN in inverter-fed electrical machines, the switching losses of the power electronics can be reduced. However, this leads to steeper voltage gradients, resulting in a strongly nonlinear transient potential distribution along the winding of the electrical machine. As a result, the insulation system – especially the turn-to-turn insulation – is subjected to additional voltage stress. To carry out targeted dimensioning of the insulation system, it is necessary to calculate the transient potential distribution in advance. In the design of a hairpin winding, it is possible to influence the transient potential differences by employing a method called “shifting” within the winding scheme and thus to reduce the maximum potential differences that occur. On this basis, a targeted design of winding plans with hairpins can be achieved. Here, both the transient potential differences between the conductors within a slot of the stator core and the potential differences between the conductors of different phases in the end winding region of the machine are considered. Furthermore, the voltage differences between the conductors and the stator core are determined and compared for different variants. In this way, it is possible to reduce the amount of material used in the insulation system. Finally, an advantageous winding layout plan based on reduced potential differences is compared with a reference plan.
Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty
Authors: Kihara Shinsuke , Kanzaki Noriyuki , Yamashita Takahiro , Yamamoto Tetsuya , Nishida Kyohei , Nagai Kanto , Araki Daisuke , Hoshino Yuichi , Matsushita Takehiko , Kuroda Ryosuke
Published: March 2023

Purpose

This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA).

Methods

This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated.

Results

The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007).

Conclusion

In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.
Design of colorimetric nanostructured sensor phases for simple and fast quantification of low concentrations of acid vapors
Authors: Fernández-Ramos M. D. , Bastida-Armesto M. , Blanc-García R. , Capitán-Vallvey L. F. , Medina-Castillo A. L.
Published: March 2023

Two colorimetric nanostructured sensor phases (Color-NSPs) for the determination of low concentrations of acid vapors in the atmosphere of paper storage rooms have been designed and characterized. The acid vapor determination is based on the color change that occurs in polyaniline (PANI) in the presence of acids when it goes from its emeraldine base form (blue) to its emeraldine salt form (green). To synthesize the Color-NSPs, two methods have been used, a one-step method performed by grafting polyaniline onto a cellulose membrane (Cellu-PANI) and a two-step method in which in the first step, polyaniline is grafted onto the surface of polymeric nanoparticles (NPs-PANI), and in a second step, NPs-PANI are immobilized into the pores of a nylon membrane (Nylon-NPs PANI). The response of the sensors versus acid vapor was measured by color coordinates with a photographic camera. A linear response range from 1 ppmv to 7 ppmv was found for both sensors, and the detection limits were 0.95 ppmv (1.2 % RSD) and 0.40 ppmv (0.8 % RSD) for Cellu-PANI and Nylon-NPs PANI, respectively. In addition, both sensors showed complete reversibility and a short exposition time (5 min). The potential applicability of the Color-NSPs in the control of the exposure of paper heritage collections to outdoor- and indoor-generated gaseous pollutants was demonstrated by determining acid vapors in museums. The method was validated with an external reference method; the paired test was applied, andp-values greater than 5% were obtained, indicating an excellent correlation and showing that the Color-NSPs reported are simple, fast, and an economical alternative to control and protect cultural heritage materials in indoor environments.

Graphical Abstract
Inter-implant distance and buccal bone thickness for a novel implant design: a preclinical study
Authors: Chen Stephen , Darby Ivan
Published: March 2023

Objectives

This study assessed bone height between novel tapered implants at different inter-implant thread peak (TP) distances, and the impact of TP distance from outer buccal bone (BB) on marginal bone levels (MBL).

Materials and Methods

Fully tapered implants with 0.5-mm thread depth and TP diameter 1 mm wider than the shoulder diameter were placed in healed ridges of minipigs. On one side, four implants were placed with inter-implant TP distances of 1, 2, or 3 mm corresponding to inter-implant implant shoulder distances of 2, 3, and 4 mm respectively. Three implants were placed on the other side with TP distances to outer BB of > 1 mm, 0.5–1 mm, or < 0.5 mm. After 12 weeks, (a) first bone-to-implant contact (fBIC), total BIC, bone area-to-total area (BATA), and coronal bone height between implants (Bi ½ max) for inter-implant distance, and (b) fBIC, BIC, and perpendicular crest to implant shoulder (pCIS) for BB were evaluated.

Results

No significant differences in bone healing and inter-implant bone height were noted for any of the TP distances. BB resorption was significant when TP distance to outer BB was < 0.5 mm. However, fBIC was lowest with TP to outer BB of 1.75 mm.

Conclusions

Inter-implant bone height between adjacent implants can be maintained even at an inter-implant TP distance as low as 1 mm. A minimum TP to outer BB distance of 0.75 mm is required for predictable maintenance of MBL.

Clinical relevance

Inter-implant distance and BB thickness are clinically relevant and require preclinical research to clarify concepts.
Simultaneous determination of dehydroacetic acid, benzoic acid, sorbic acid, methylparaben and ethylparaben in foods by high-performance liquid chromatography
Authors: So Ji Sun , Lee Soo Bin , Lee Jin Hye , Nam Hye Seon , Lee Jong Kwon
Published: March 2023

In this study, an analytical method was established and validated to determine the preservatives such as dehydroacetic acid, benzoic acid, sorbic acid, methylparaben and ethylparaben. The level of preservatives was measured by solvent extraction method adding purification process with carrez reagent and by high-performance liquid chromatography (HPLC). The developed analytical method was successfully applied to determine the concentration of preservatives in various food samples including jam, cheese and soy sauce, displaying high accuracy (recoveries between 87.8% and 110%) and precision (%RSD less than 5.92% and 7.72% for intra-day and inter-day, respectively). To verify the applicability of the improved test method, selected 13 food items and collected 521 samples were monitored. As a result, all the cases met the Korea standard guidelines. Consequently, this study is expected to contribute to the safety management of preservatives for domestic distribution and imported food.
Fissurectomy versus lateral internal sphincterotomy in the treatment of chronic anal fissures: no advantages in terms of post-operative incontinence
Authors: Tutino Roberta , Nigro Casimiro , Paternostro Flavia , Federico Rosa , Lo Secco Giacomo , Gallo Gaetano , Santarelli Mauro , Cocorullo Gianfranco , Bonventre Sebastiano
Published: March 2023

Purpose

The standard treatment for chronic anal fissures that have failed non-operative management is lateral internal sphincterotomy. Surgery can cause de novo incontinence. Fissurectomy has been proposed as a sphincter/saving procedure, especially in the presence of a deep posterior pouch with or without a crypt infection. This study investigated whether fissurectomy offers a benefit in terms of de novo post-operative incontinence.

Methods

Patients surgically managed with fissurectomy or lateral internal sphincterotomy for chronic anal fissures from 2013 to 2019 have been included. Healing rate, changes in continence and patient satisfaction were investigated at long-term follow-up.

Results

One hundred twenty patients (55 females, 65 males) were analysed: 29 patients underwent fissurectomy and 91 lateral internal sphincterotomy. Mean follow-up was 55 months [confidence interval (CI) 5–116 months]. Both techniques showed some rate of de novo post-operative incontinence (> +3 Vaizey score points): 8.9% lateral internal sphincterotomy, 17.8% fissurectomy (p = 0.338). The mean Vaizey score in these patients was 10.37 [standard deviation (sd) 6.3] after lateral internal sphincterotomy (LIS) and 5.4 (sd 2.3) after fissurectomy Healing rate was 97.8% in the lateral internal sphincterotomy group and 75.8% in the fissurectomy group (p = 0.001). In the lateral internal sphincterotomy group, patients with de novo post-op incontinence showed a statistically significant lower satisfaction rate (9.2 ± 1.57 versus 6.13 ± 3; p = 0.023) while no differences were present in the fissurectomy group (8.87 ± 1.69 versus 7.4 ± 1.14; p = 0.077).

Conclusions

Lateral internal sphincterotomy is confirmed as the preferred technique in term of healing rate. Fissurectomy did not offer a lower rate of de novo post-operative incontinence, but resulted in lower Vaizey scores in patients in whom this occurred. Satisfaction was lower in patients suffering a de novo post-operative incontinence after lateral internal sphincterotomy.
Profiling of kidney involvement in systemic lupus erythematosus by deep learning using the National Database of Designated Incurable Diseases of Japan
Authors: Kimura Tomonori , Ikeuchi Hidekazu , Yoshino Mitsuaki , Sakate Ryuichi , Maruyama Shoichi , Narita Ichiei , Hiromura Keiju
Published: March 2023

Background

Kidney involvement frequently occurs in systemic lupus erythematosus (SLE), and its clinical manifestations are complicated. We profiled kidney involvement in SLE patients using deep learning based on data from the National Database of Designated Incurable Diseases of Japan.

Methods

We analyzed the cross-sectional data of 1655 patients with SLE whose Personal Clinical Records were newly registered between 2015 and 2017. We trained an artificial neural network using clinical data, and the extracted characteristics were evaluated using an autoencoder. We tested the difference of population proportions to analyze the correlation between the presence or absence of kidney involvement and that of other clinical manifestations.

Results

Data of patients with SLE were compressed in a feature space in which the anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody titer, antinuclear antibody titer, or white blood cell count contributed significantly to distinguishing patients. Many SLE manifestations were accompanied by kidney involvement, whereas in a subgroup of patients with high anti-dsDNA antibody titers and low antinuclear antibody titers, kidney involvement was positively and negatively correlated with hemolytic anemia and inflammatory manifestations, respectively.

Conclusion

Although there are various combinations of SLE manifestations, our study revealed that some of them are specific to kidney involvement. SLE profiles extracted from the objective analysis will be useful for categorizing SLE manifestations.
Nuclear Translocation Triggered at the Onset of Hearing in Cochlear Inner Hair Cells of Rats and Mice
Authors: Iyer Megana R. , Kalluri Radha
Published: March 2023

Purpose

Nuclear position is precisely orchestrated during cell division, migration, and maturation of cells and tissues. Here we report a previously unrecognized, programmed movement of the nucleus in rat and mouse cochlear inner hair cells (IHCs) coinciding with the functional maturation of inner hair cells around the onset of hearing.

Methods

We measured hair cell length and nuclear position from confocal scans of immunofluorescence-labeled hair cells from whole-mount cochlear preparations throughout post-natal development.

Results

In early post-natal days, the IHC experiences a period of sustained growth, during which the nucleus sits at the very basal pole of the cell, far from the apically located mechano-transducing stereocilia, but close to where synapses with primary afferent and efferent neurons are forming. After IHCs reach their final length, the nucleus moves to occupy a new position half-way along the length of the cell. Nuclear translocation begins in the middle turn, completes throughout the cochlea within 2–3 days, and coincides with the emergence of endolymphatic potential, the acquisition of big-conductance potassium channels (BK), and the onset of acoustic hearing. IHCs cultured in-vitro without endolymphatic potential (EP) do not grow, do not express BK, and do not experience nuclear movement. IHCs cultured in high K+ solutions (to simulate EP) grow but do not experience nuclear movement or acquire BK channels.

Conclusion

Nuclear migration at the onset of hearing is a key step in the morphological maturation of IHCs. Whether this plays a role in functional maturation remains to be explored.
A mobile e-learning application for enhancement of basic mathematical skills in visually impaired children
Authors: Shoaib Muhammad , Khan Shakeel , Fitzpatrick Donal , Pitt Ian
Published: March 2023

Although smartphones are equipped with accessibility functions, they still pose significant problems for visually impaired people. Sometimes these functions cannot fulfil the expectations of users. Early mobile devices had physical buttons and a keypad, and visually impaired users could navigate around the keypad using the tactile markers on the buttons. However, the lack of tactile markers makes it much more difficult to operate a touchscreen device. This paper describes an e-learning platform that is designed to improve the accessibility of smartphone applications for students who are visually impaired but have some useful vision. A User-Centered Design approach was used to develop an effective solution for visually impaired students. A study was conducted during the development of the described platform, and the results showed that our suggested design improves task completion time as compared to the initial version. Participants also expressed higher levels of satisfaction when using the improved design of this platform. The modified design was also assessed using the Mobile Application Rating Scale (MARS), and the results indicate that it is quite reliable and rated well among visually impaired children. Furthermore, developers can use our suggested design guidelines such as clear navigation, color contrast, immediate feedback, icon arrangements, button and text size in the development of new applications.
Predictive structure building in language comprehension: a large sample study on incremental licensing and parallelism
Authors: Fujita Hiroki
Published: March 2023

In online language comprehension, the parser incrementally builds hierarchical syntactic structures. The predictive nature of this structure-building process has been the subject of extensive debate. A previous study observed that when a wh-phrase indicates parallelism between the upcoming wh-clause and a preceding clause (e.g.,John told some stories, but we couldn’t remember which stories…), the parser predictively constructs the wh-clause. This observation demonstrates predictive structure building. However, the study also suggests that the parser does not make a prediction when the wh-phrase indicates that parallelism does not hold (e.g.,John told some stories … with which stories…), a potential limit to the prediction of syntactic structures. Crucially, these findings are controversial because the study did not observe processing difficulty when disambiguating input indicated that the predicted continuation was inconsistent with the globally grammatical structure (garden-path effects). The controversial results may be due to a lack of statistical power. Therefore, the present study conducted a large-scale replication study (324 participants and 24 sets of materials). The results revealed that the parser predicts the clausal structure, irrespective of the type of wh-phrase. There was also evidence of garden-path effects, supporting the finding that the parser makes a prediction. These observations suggest that the prediction algorithm inherent in the human parser is more powerful than assumed by the previous study and that the parser attempts to construct globally grammatical structures during revision.
Restoring mixed forests through conversion of Norway spruce stands: effects of fencing and mechanical site preparation on performance of planted beech and natural tree regeneration
Authors: Löf Magnus , Sandell Festin Emma , Szydło Mateusz , Brunet Jörg
Published: March 2023

Conversion of Norway spruce (Picea abies) plantations to more diverse and resilient forest types is an important task for European forest managers in the face of climate change and increased focus on ecosystem services beyond timber production. However, there is a lack of knowledge on how to cost-effectively restore such forests. This study reports the influence of vicinity (distance) of forest type (mixed or spruce), fencing and mechanical site preparation (MSP) on the early performance of planted beech (Fagus sylvatica) seedlings and natural regeneration of other tree species following clear-cuts of Norway spruce in southern Sweden. After 6 years, we found clear effects of fencing and MSP, but not of vicinity of forest type. Fencing had a positive effect on height growth of Scots pine (Pinus sylvestris) but not on height of planted beech and naturally regenerated birch (Betula pendula,B. pubescens). There was a positive effect of MSP on survival and height growth of planted beech, and on the amount of natural regeneration of Scots pine. We conclude that establishment of beech forest is greatly accelerated by active regeneration approaches such as planting. In addition, the combination of planting beech, natural regeneration of other species, fencing and MSP is effective to promote the transition to mixed and diverse stands with both broadleaves and conifers. Fencing represented the highest cost among the treatments, and its cost-effectiveness depends on the local ungulate browsing pressure. In our study, fencing was critical to protect natural regeneration of Scots pine from browsing. Finally, natural regeneration of birch was abundant in our study and relatively unaffected by fencing and MSP treatments. With time, pre-commercial thinning of the naturally regenerated birch will be needed to maintain a diverse mixture of tree species.
A standalone prediction model for atomic oxygen and coronal mass ejections
Authors: Mahmoud W. M. , Elfiky D. , Robaa S. M. , Elnawawy M. S. , Yousef S. M.
Published: March 2023

This paper presents a standalone predictive model for Atomic Oxygen (AO), Coronal Mass Ejections (CMEs) and other space-environment parameters. The prediction is based on the numerical method of Holt–Winter’s triple smooth exponential forecasting of atmospheric constituents. Solar cycle 25 is likely to show about the same activity as cycle 23. The corresponding AO-flux–solar-activity correlation coefficients for altitudes 100, 200, and 300 km are: 0.62, 0.53, and 0.48, respectively, while the correlation coefficients for higher altitudes are lower than 0.48, an advantage that makes them more favorable for LEOs due to the harmful corrosive effects.
Finnish parliament ASR corpus
Authors: Virkkunen Anja , Rouhe Aku , Phan Nhan , Kurimo Mikko
Published: March 2023

Public sources like parliament meeting recordings and transcripts provide ever-growing material for the training and evaluation of automatic speech recognition (ASR) systems. In this paper, we publish and analyse the Finnish Parliament ASR Corpus, the most extensive publicly available collection of manually transcribed speech data for Finnish with over 3000 h of speech and 449 speakers for which it provides rich demographic metadata. This corpus builds on earlier initial work, and as a result the corpus has a natural split into two training subsets from two periods of time. Similarly, there are two official, corrected test sets covering different times, setting an ASR task with longitudinal distribution-shift characteristics. An official development set is also provided. We developed a complete Kaldi-based data preparation pipeline and ASR recipes for hidden Markov models (HMM), hybrid deep neural networks (HMM-DNN), and attention-based encoder-decoders (AED). For HMM-DNN systems, we provide results with time-delay neural networks (TDNN) as well as state-of-the-art wav2vec 2.0 pretrained acoustic models. We set benchmarks on the official test sets and multiple other recently used test sets. Both temporal corpus subsets are already large, and we observe that beyond their scale, HMM-TDNN ASR performance on the official test sets has reached a plateau. In contrast, other domains and larger wav2vec 2.0 models benefit from added data. The HMM-DNN and AED approaches are compared in a carefully matched equal data setting, with the HMM-DNN system consistently performing better. Finally, the variation of the ASR accuracy is compared between the speaker categories available in the parliament metadata to detect potential biases based on factors such as gender, age, and education.
Segmentation and Classification Approaches of Clinically Relevant Curvilinear Structures: A Review
Authors: KV Rajitha , Prasad Keerthana , Peralam Yegneswaran Prakash
Published: March 2023

Detection of curvilinear structures from microscopic images, which help the clinicians to make an unambiguous diagnosis is assuming paramount importance in recent clinical practice. Appearance and size of dermatophytic hyphae, keratitic fungi, corneal and retinal vessels vary widely making their automated detection cumbersome. Automated deep learning methods, endowed with superior self-learning capacity, have superseded the traditional machine learning methods, especially in complex images with challenging background. Automatic feature learning ability using large input data with better generalization and recognition capability, but devoid of human interference and excessive pre-processing, is highly beneficial in the above context. Varied attempts have been made by researchers to overcome challenges such as thin vessels, bifurcations and obstructive lesions in retinal vessel detection as revealed through several publications reviewed here. Revelations of diabetic neuropathic complications such as tortuosity, changes in the density and angles of the corneal fibers have been successfully sorted in many publications reviewed here. Since artifacts complicate the images and affect the quality of analysis, methods addressing these challenges have been described. Traditional and deep learning methods, that have been adapted and published between 2015 and 2021 covering retinal vessels, corneal nerves and filamentous fungi have been summarized in this review. We find several novel and meritorious ideas and techniques being put to use in the case of retinal vessel segmentation and classification, which by way of cross-domain adaptation can be utilized in the case of corneal and filamentous fungi also, making suitable adaptations to the challenges to be addressed.
A Comparison of the Volumetric Properties of Proteated and Deuterated Water and Their Relation to Other Thermodynamic Properties
Authors: Fucaloro Anthony F. , Zanella Andrew
Published: March 2023

The unusual volumetric properties of both proteated and deuterated water are explored by carefully comparing their volumetric properties and developing a heuristic molecular model to describe the behavior. The behavior is further explored by relating these properties to other well-known thermodynamic properties.
Effects of Interferon-γ and Interleukin-4 on Proliferating Cell Nuclear Antigen Expression in Transplanted Bone Tumor Tissue
Authors: Lv Jiaxing , Ji Jianjun , Bai Leipeng , Xu Ying , Su Zhenyan , Jin Yu
Published: March 2023

The rabbit VX2 bone tumor model is an ideal animal model for studying malignant bone tumors. Cytokines have been reported to play a role in tumor initiation and promotion, angiogenesis, and metastasis. However, few studies have investigated the relationship between cytokines and VX2 bone tumor development. This study investigated the effect of interferon-γ (IFN-γ) and interleukin-4 (IL-4) on proliferating cell nuclear antigen (PCNA) expression in tumor tissue. Thirty Japanese white rabbits were randomly divided into group A (n = 15) and group B (n = 15). The rabbit VX2 bone tumor model was constructed by implanting VX2 tumors on the medial side of the upper tibia. Group A was sacrificed in the first week of implantation, and group B in the second week of implantation. Peripheral venous blood, tumor tissue from the medullary cavity at the implantation site, and surrounding bone and soft tissue were harvested before implantation and execution in both experimental groups. IFN-γ and IL-4 expression levels in peripheral blood and PCNA levels in tumor tissues were measured by enzyme-linked immunosorbent assay (ELISA). The tumor tissue of the medullary cavity and surrounding bone and soft tissue was harvested for pathological examination. By the end of the experiment, 30 rabbits were included in the study. There was no significant difference in IFN-γ, IL-4 and PCNA expression levels in group A compared to group B before implantation (t = 1.187, p value = 0.255; t = 1.282, p value = 0.221; t = 0.499, p value = 0.626). IFN-γ and IL-4 expression levels before execution in group A were not significantly different from those before implantation (t = -1.280, p value = 0.213; t = 0.952, p value = 0.349), and PCNA expression levels were higher than those before implantation (t = 2.469, p value = 0.020). Group B had significantly lower IFN-γ expression levels before execution than before implantation (t = -3.741, p value = 0.001) and significantly higher IL-4 and PCNA expression levels before execution than before implantation (t = 6.279, p value < 0.01; t = 13.031, p value < 0.001). IFN-γ expression levels before execution in group B was significantly lower than those before execution in group A (t = 17.184, p value < 0.001), and IL-4 and PCNA expression before execution in group B was significantly higher than that before execution in group A (t = -26.235, p value < 0.001; t = -24.619, p value < 0.001). The correlation between IFN-γ and PCNA levels before execution in groups A and B was negative (r = -0.566, p value = 0.028; r = -0.604, p value = 0.017), and the correlation between IL-4 and PCNA levels was positive (r = 0.583, p value = 0.023; r = 0.884, p value < 0.001). In the rabbit VX2 bone tumor model, extending the period of time after tumor implantation resulted in a negative correlation between IFN-γ and PCNA levels and a positive correlation between IL-4 and PCNA levels.
Provision of drug and alcohol services amidst COVID-19 pandemic: a qualitative evaluation on the experiences of service providers
Authors: Richards-Jones Levi , Patel Priya , Jagpal Parbir Kaur , Lowrie Richard , Saunders Karen , Burwood Sarah , Shrestha Sunil , Paudyal Vibhu
Published: March 2023

Background

The impact of COVID-19 pandemic on the provision of drug and alcohol (D&A) services and associated outcomes have been under-researched.

Aim

This study aimed to understand the experiences of service providers in relation to how drug and alcohol (D&A) services were affected during COVID-19 pandemic, including the adaptations made and lessons learnt for the future.

Method

Focus groups and semi-structured interviews were conducted with participants from various D&A service organisations across the UK. Data were audio recorded, followed by transcription and thematic analysis.

Results

A total of 46 participants representing various service providers were recruited between October and January 2022. The thematic analysis identified ten themes. COVID-19 required significant changes to how the treatment was provided and prioritised. Expansion of telehealth and digital services were described, which reduced service wait times and increased opportunities for peer network. However, they described missed opportunities for disease screening, and some users risked facing digital exclusion. Participants who provided opiate substitution therapy service spoke of improving service provider/user trust following the shift from daily supervised treatment consumption to weekly dispensing. At the same time, they feared fatal overdoses and non-adherence to treatment.

Conclusion

This study demonstrates the multifaceted impact of the COVID-19 pandemic on UK-based D&A service provisions. The long-term impact of reduced supervision on Substance Use Disorder treatment and outcomes and any effect of virtual communications on service efficiency, patient-provider relationships and treatment retention and successes are unknown, suggesting the need for further study to assess their utility.