bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of external tissue expansion technique in the treatment of soft tissue defects: a systematic review and meta-analysis of outcomes and complication rates
Authors: Tong Xirui , Lu Jianyu , Zhang Wei , Wang Siqiao , Huang Runzhi , Zhang Xianliang , Huang Jie , Zhu Yushu , Xiao Shichu , Ji Shizhao , Xia Zhaofan
Published: December 2022

Background

Currently, various external tissue expansion devices are becoming widely used. Considering the scarcity of relevant application standards, this systematic review was performed to explore the effectiveness and safety of external tissue expansion techniques for the reconstruction of soft tissue defects.

Method

A systematic review and meta-analysis on the efficacy and safety of external tissue expansion technique was conducted. A comprehensive search was performed in the following electronic databases: PubMed/Medline, Embase, Cochrane Library (Wiley Online Library), and Web of Science. Studies reporting patients with soft tissue defects under the treatment of external tissue expansion technique were included.

Results

A total of 66 studies with 22 different types of external tissue expansion devices met the inclusion criteria. We performed a descriptive analysis of different kinds of devices. A single-arm meta-analysis was performed to evaluate the efficacy and safety of the external tissue expansion technique for different aetiologies. The pooled mean wound healing time among patients with defects after fasciotomy was 10.548 days [95% confidence interval (CI) = 5.796–15.299]. The pooled median wound healing times of patients with defects after excisional surgery, trauma, chronic ulcers and abdominal defects were 11.218 days (95% CI = 6.183-16.253), 11.561 days (95% CI = 7.062-16.060), 15.956 days (95% CI = 11.916-19.996) and 12.853 days (95% CI=9.444-16.227), respectively. The pooled wound healing rates of patients with defects after fasciotomy, excisional surgery, trauma, chronic ulcers and abdominal defects were 93.8% (95% CI=87.1-98.2%), 97.2% (95%CI=92.2-99.7%), 97.0% (95%CI=91.2-99.8%), 99.5% (95%CI=97.6-100%), and 96.8% (95%CI=79.2-100%), respectively. We performed a subgroup analysis in patients with diabetic ulcers and open abdominal wounds. The pooled median wound healing time of patients with diabetic ulcers was 11.730 days (95% CI = 10.334-13.125). The pooled median wound healing time of patients with open abdomen defects was 48.810 days (95% CI = 35.557–62.063) and the pooled successful healing rate was 68.8% (95% CI = 45.9-88.1%). A total of 1686 patients were included, 265 (15.7%) of whom experienced complications. The most common complication was dehiscence (n = 53, 3.14%).

Conclusions

Our systematic review is the first to demonstrate the efficacy and safety of external tissue expansion in the management of soft tissue defects. However, we must interpret the meta-analysis results with caution considering the limitations of this review. Large-scale randomized controlled trials and long-term follow-up studies are still needed to confirm the effectiveness and evaluate the quality of healing.
Clinico-pathological correlations and outcomes of de novo glomerular diseases in patients after haematopoietic stem cell transplantation
Authors: Yap Desmond Y H , Lie Davina , Lau Tiffany , Tang Alex , Chan Gavin , Chan Thomas S Y , Sim Joycelyn , Lie Albert K W , Chan Tak Mao
Published: December 2022

Background

Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited.

Methods

We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999.

Results

A total of 2204 patients underwent HSCT during the period 1999–2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin–angiotensin–aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years.

Conclusion

De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.
Rationale for the evaluation of renal functional reserve in allogeneic stem cell transplantation candidates: a pilot study
Authors: Mancianti Nicoletta , Guarnieri Andrea , Lenoci Mariapia , Toraldo Francesca , Salvo Domenica Paola , Belluardo Massimo , Iadanza Ernesto , Ferretti Fabio , Marotta Giuseppe , Garosi Guido
Published: December 2022

Background

The main purpose of our study was to evaluate the ability of renal functional reserve (RFR) to stratify the risk of acute kidney injury (AKI) occurrence within 100 days of hematopoietic stem cell transplantation (HSCT) and to predict any functional recovery or the onset of chronic kidney disease. A secondary aim was to identify the clinical/laboratory risk factors for the occurrence of AKI.

Methods

The study design is prospective observational. We enrolled 48 patients with normal basal glomerular filtration rate (bGFR) who underwent allogenic HSCT. A multiparameter assessment and the Renal Functional Reserve Test (RFR-T) using an oral protein load stress test were performed 15 days before the HSCT.

Results

Different RFRs corresponded to the same bGFR values. Of 48 patients, 29 (60%) developed AKI. Comparing the AKI group with the group that did not develop AKI, no statistically significant difference emerged in any characteristic related to demographic, clinical or multiparameter assessment variables except for the estimated GFR (eGFR). eGFR ≤100 mL/min/1.73 m2 was significantly related to the risk of developing AKI (Fisher’s exact test, P = .001). Moreover, RFR-T was lower in AKI+ patients vs AKI– patients, but did not allow statistical significance (28% vs 40%). In AKI patients, RFR >20% was associated with complete functional recovery (one-sided Fisher’s exact test, P = .041). The risk of failure to recover increases significantly when RFR ≤20% (odds ratio = 5.50, 95% confidence interval = 1.06–28.4).

Conclusion

RFR identifies subclinical functional deterioration conditions essential for post-AKI recovery. In our cohort of patients with no kidney disease (NKD), the degree of pre-HSCT eGFR is associated with AKI risk, and a reduction in pre-HSCT RFR above a threshold of 20% is related to complete renal functional recovery post-AKI. Identifying eGFR first and RFR second could help select patients who might benefit from changes in transplant management or early nephrological assessment.
Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials
Authors: Laborante Renzo , Bianchini Emiliano , Restivo Attilio , Ciliberti Giuseppe , Galli Mattia , Vergallo Rocco , Rodolico Daniele , Zito Andrea , Princi Giuseppe , Leone Antonio Maria , Aurigemma Cristina , Romagnoli Enrico , Montone Rocco Antonio , Burzotta Francesco , Trani Carlo , Crea Filippo , D'Amario Domenico
Published: December 2022

Aims

Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization.

Methods and results

PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0–1 and TIMI flow grade 0–2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size.

Conclusion

Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.
Inputs don't equal outputs: bacterial microbiomes of the ingesta, gut, and feces of the keystone deposit feeder Ilyanassa obsoleta
Authors: Plante Craig J , Hill-Spanik Kristina M , Emerson Rowan
Published: December 2022

Bacteria drive energy fluxes and geochemical processes in estuarine sediments. Deposit-feeding invertebrates alter the structure and activity of microbial communities through sediment ingestion, gut passage, and defecation. The eastern mud snail, Ilyanassa obsoleta, is native to estuaries of the northwestern Atlantic, ranging from Nova Scotia, Canada, to Florida in the USA. Given extremely high densities, their deposit-feeding and locomotory activities exert ecological influence on other invertebrates and microbes. Our aim was to characterize the bacterial microbiome of this ‘keystone species’ and determine how its feeding alters the native bacterial microbiota. We gathered snails from both mudflat and sandflat habitats and collected their fresh fecal pellets in the laboratory. Dissection of these same snails allowed us to compare bacterial assemblages of ingested sediments, shell surfaces, gut sections (esophagus, stomach, intestine), and feces using DNA metabarcoding. Our findings indicate a diverse, resident gut microbiota. The stomach and intestines were dominated by bacteria of the genus Mycoplasma. Comparison of ingesta and feces revealed digestion of several bacterial taxa, introduction of gut residents during passage, in addition to unique bacterial taxa within the feces of unknown provenance. Our results demonstrate that I. obsoleta has the potential to modify microbial community structure in estuarine sediments.
Stand-Density Effects on Aboveground Carbon Dynamics in SecondaryPinusandQuercusForests of Central USA
Authors: Anderson Samantha , Knapp Benjamin O , Kabrick John M
Published: December 2022

Temperate forests play an important role in the sequestration and storage of carbon. We evaluated the long-term effects of manipulating stand density on aboveground live tree carbon dynamics and volume production for separate pine (Pinus spp.) and oak (Quercus spp.) forests of central USA. For both species groups, stand-level carbon storage in standing live trees was greatest without management, with unthinned pine plateauing around 100 Mg/ha of carbon at approximately 50 years old and the oak stands increasing to around 100 Mg/ha of carbon by about 80 years old. In the pine stands, stand-level carbon sequestration was greatest in stands that were thinned but maintained fully stocked conditions. Consequently, the gross carbon that accumulated during the study period, which included standing carbon in live trees and carbon from trees that were harvested or otherwise died, was maximized when stand stocking was maintained at an average of around 80% stocking during the study period. These results were compatible with the production of sawtimber volume, which was greatest for stands that were maintained in fully stocked but not overstocked conditions. Our results demonstrate that thinning can be a forest management strategy to achieve multiple objectives, including those for carbon management and sawtimber production.

Study Implications: Our results support stand-density management (i.e., thinning) as a forestry practice compatible with carbon objectives and more traditional objectives of timber production. Aboveground carbon stored in live trees was greatest without thinning, but gross production and sequestration rates were greatest when stand density was maintained in fully stocked but not overstocked conditions. Active forest management during stand development can provide managers with the flexibility to address multiple objectives and may be used with other carbon management practices such as extended rotations or continuous canopy cover, particularly in the central and northeastern United States where forests are generally aging uniformly throughout the region.
The Association of Peripheral and Central Olfaction With Frailty in Older Adults
Authors: Nagururu Nimesh V , Bernstein Isaac A , Voegtline Kristin , Olson Sarah , Agrawal Yuri , Rowan Nicholas R
Published: December 2022

Background

Olfactory impairment is increasingly recognized as a biomarker of frailty, but the relationship between olfactory subdomains that describe peripheral or central dysfunction and frailty remains unexplored.

Methods

We examined 1 160 older adults from the National Social Life, Health, and Aging Project Wave 3. Olfactory identification (OI): the ability to identify an odorant; and olfactory sensitivity (OS): the ability to detect the presence of an odorant, were assessed using 5- and 6-point measures, respectively. Frailty was operationalized as both a 37-item frailty index (FI) and the 5-item Physical Frailty Phenotype (PFP). Mixed models were fit to examine the association between OI, OS, FI, and PFP, while adjusting for demographic and clinical covariates.

Results

Participants in the most-frail PFP category had lower OI and OS scores (OI: 3.88 vs 4.19, p = .016; OS: 3.15 vs 3.47, p = .031), whereas participants in the most-frail FI category exhibited lower OI scores but not OS scores when compared to nonfrail participants (OI: 3.72 vs 4.27, p = .014; OS: 3.19 vs 3.43, p = .476). Adjusted mixed models showed that a point increase in OI was associated with a lower PFP score (β = −0.107, p = .006) and FI score (β = −0.009, p = .010). A point increase in OS was associated with a lower PFP score (β = −0.058, p = .016) but not FI score (β = −0.004, p = .064).

Conclusion

Both OS and OI, predominantly peripheral and central measures of olfaction, respectively, are associated with frailty implicating olfaction as a potential biomarker and risk factor for frailty.
Detecting the January 15, 2022 Hunga Tonga-Hunga-Ha'apai volcanic eruption (SW Pacific) high up in the sky through “ionospheric resonance”
Authors: Kundu Bhaskar , Senapati Batakrushna , Bürgmann Roland , Ray Sayak
Published: December 2022

We report a mode of ionospheric resonance induced by the January 15, 2022, Hunga Tonga-Hunga-Ha'apai volcanic eruption, captured globally through ground-based GNSS networks. In the near-field region, we observe a strong ionospheric disturbance in the total electron content, including contributions from acoustic waves and gravity waves. In contrast, propagation of gravity waves, seismic airwaves diffracted by topographic barriers, and/or atmospheric Lamb waves can be documented for far-field ionospheric disturbances. Specifically, the atmospheric wave propagation towards the Hawaii Islands involved three distinct modes of ionospheric perturbation through Rayleigh wave, gravity waves and atmospheric Lamb waves. Further, we also noticed that the peak-to-peak amplitude of the disturbance reached ∼ 8.7 per cent of the background electrons, which is significantly higher than the recent volcanic explosions in the Japanese Islands and the 2020 chemical explosion in Beirut. The ionospheric total electron content perturbations can provide important information about the volcanic source, hence they could be useful as a measure of eruption intensity and for real-time hazard monitoring.
Higher Rank Brill–Noether Theory on ℙ2
Authors: Gould Ben , Liu Yeqin , Lee Woohyung
Published: December 2022

Let $M_{{\mathbb {P}}^{2}}(\textbf {v})$ be a moduli space of semistable sheaves on ${\mathbb {P}}^{2}$, and let $B^{k}(\textbf {v}) \subseteq M_{{\mathbb {P}}^{2}}(\textbf {v})$ be the Brill–Noether locus of sheaves $E$ with $h^{0}({\mathbb {P}}^{2}, E) \geq k$. In this paper, we develop the foundational properties of Brill–Noether loci on ${\mathbb {P}}^{2}$. Set $r = r(E)$ to be the rank and $c_{1}, c_{2}$ the Chern classes. The Brill–Noether loci have natural determinantal scheme structures and expected dimensions $\dim B^{k}(\textbf {v}) = \dim M_{{\mathbb {P}}^{2}}(\textbf {v}) - k(k - \chi (E))$. When $c_{1}> 0$, we show that the Brill–Noether locus $B^{r}(\textbf {v})$ is nonempty. When $c_{1} = 1$, we show all of the Brill–Noether loci are irreducible and of the expected dimension. We show that when $\mu = c_{1}/r> 1/2$ is not an integer and $c_{2} \gg 0$, the Brill–Noether loci are reducible and describe distinct irreducible components of both expected and unexpected dimension.
Comparative Evaluation of Carboxyhemoglobin Quantification in Postmortem Whole Blood by CO-Oximetry and Headspace Gas Chromatography with Flame Ionization Detection and Atom Absorption Spectrophotometry
Authors: Kristoffersen Lena , Vevelstad Merete , Hansen Inger-Ann , Strømsvåg Berit , Strand Dag Helge
Published: December 2022

A comparative evaluation of two methods used for carboxyhemoglobin (COHb) determination in postmortem whole blood was performed: carbon monoxide (CO)-oximetry measuring at 128 wavelengths and headspace gas chromatography with flame ionization detection (HS-GC--FID) where CO was determined after catalytic reduction of CO to CH4 and Fe was determined by atom absorption spectrophotometry (AAS, 248.3 nm). An aliquot of 100 µL whole blood was loaded into the CO-oximetry module. In the HS-GC--FID analysis, to 1.0 mL of whole blood, 3.0 mL of saponin solution was added, mixed and centrifuged. To 20 mL HS vials, 400 µL of the supernatant was added and the vials were immediately sealed. One milliliter of potassium hexacyanoferrat (III) solution was added through the HS septum and mixed. The samples were incubated at 70°C for 5 min. CO was separated using He as carrier gas and a CP-Molsieve 5 Å PLOT capillary column. Fe was determined using 400 µL of the saponin supernatant diluted to 10 mL by water. During a period of ∼3 years, 124 postmortem whole blood samples were analyzed. Bland–Altman method comparison showed satisfactory agreement and no significant bias between the methods for the whole saturation range (5 to 85% COHb). Five samples, all with %COHb >40, showed deviations of more than 10% COHb in absolute terms. One sample, in the lower COHb range <10%, was false negative on the CO-oximetry method. The between-assay accuracy, reported as bias, at 60% COHb was −0.8% and −9.0%, and precision, reported as relative standard deviation, was 1.6% and 7.7%, for the CO-oximetry and HS-GC--FID-AAS methods, respectively. Both methods obtained satisfactory results in proficiency testing rounds, with z-scores <±2 (n = 11). This study showed that the CO-oximetry method based on the 128-wavelength principle and the HS-GC--FID-AAS method are comparable and satisfactory for %COHb determination in postmortem whole blood.
RNAi machinery regulates nutrient metabolism and fluconazole resistance in the pathogenic fungusCryptococcus deneoformans
Authors: Ma Xiaoyu , Li Chenxi , Ma Lan , Zhao Xuan , Liu Yanjie , Hao Xiaoran , Zhang Ping , Zhu Xudong
Published: December 2022

The RNAi machinery has been extensively studied in plant and animal cells for their crucial roles in the regulation of genome function. However, the potential roles of RNAi in controlling fungal growth and development have been poorly studied, especially in the basidiomycetous yeast Cryptococcus deneoformans. To characterize the biological functions of RNAi in the pathogenic fungus, a comparative analysis of mRNA profiles using high-throughput sequencing technology was performed for the wild type and the RNAi mutants of C. deneoformans. The results revealed a clear difference in the expression of genes associated with metabolic processes in the RNAi mutants. Besides, the growth under nutrient-limited conditions was significantly reduced in the ago2Δ mutant, suggesting the essential roles of Ago2 in nutrient metabolism. Further investigations revealed the differentially expressed transporters in the RNAi mutants, in which transporters involved in fluconazole efflux were significantly up-regulated. More importantly, on account of the upregulated transporters, RNAi mutant strains developed resistance to fluconazole. By disrupting AFR1 gene using the ‘suicide’ CRISPR-Cas9 system, we verified that the upregulated ABC transporter Afr1 in the RNAi mutants contributed to the fluconazole resistance. In summary, our data demonstrate that in C. deneoformans the RNAi pathway participates in nutrient metabolism and plays a role in the repression of fluconazole resistance, which provides a deep insight into RNAi mechanisms in Cryptococcus and brings great hints for the clinical treatment of cryptococcosis.
Isotopologue pattern based data mining for selenium species from HILIC–ESI–Orbitrap–MS-derived spectra
Authors: Bierla Katarzyna , Godin Simon , Ladányi Márta , Dernovics Mihály , Szpunar Joanna
Published: December 2022

Automated and specific picking of selenium-containing molecular entities has not been an obvious option for software tools associated with electrospray high-resolution mass spectrometry (MS). In our study, a comprehensive pattern matching approach based on intra-isotopologue distance and isotopologue ratio data was critically evaluated in terms of reproducibility and selenium isotope selection on three samples, including selenized Torula yeast and the selenium hyperaccumulator plant Cardamine violifolia. Hydrophilic interaction liquid chromatography was applied to provide a one-step separation for water soluble metabolites to put an end to the need for either orthogonal setups or poor retention on reversed phase chromatography. Assistance from inductively coupled plasma–MS was taken only for chromatographic verification purposes, and the involvement of absolute mass defect (MD) data in selenometabolite-specific screening was assessed by multivariate statistical tools. High focus was placed on screening efficiency and on the validation of discovered selenized molecules to avoid reporting of artefacts. From the >1000 molecular entries detected, selenium-containing molecules were picked up with a recovery rate of >88% and a false positive rate of <10%. Isotop(ologu)e pairs of 78Se–80Se and 80Se–82Se proved to be the most performant in the detection. On the basis of accurate mass information and hypothetical deamination processes, elemental composition could be proposed for 72 species out of the 75 selenium species encountered without taking into account selenocompound databases. Absolute MD data were used to significantly differentiate a potentially sample-specific subgroup of false positive molecular entities from non-selenized and selenized entities.
Long-term peridialytic blood pressure changes are related to mortality
Authors: de Roij van Zuijdewijn Camiel L M , Rootjes Paul A , Nubé Menso J , Bots Michiel L , Canaud Bernard , Blankestijn Peter J , van Ittersum Frans J , Maduell Francisco , Morena Marion , Peters Sanne A E , Davenport Andrew , Vernooij Robin W M , Grooteman Muriel P C ,   the HDF Pooling Project investigators, Bots Michiel L , Blankestijn Peter J , Canaud Bernard , Davenport Andrew , Grooteman Muriel P C , Nubé Menso J , Peters Sanne A E , Morena Marion , Maduell Francisco , Torres Ferran , Ok Ercan , Asci Gulay , Locatelli Francesco
Published: December 2022

Background

In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated.

Methods

To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied.

Results

During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality.

Conclusion

Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.
Rare but persistent asexual reproduction explains the success of planktonic foraminifera in polar oceans
Authors: Meilland Julie , Ezat Mohamed M , Westgård Adele , Manno Clara , Morard Raphaël , Siccha Michael , Kucera Michal
Published: December 2022

The reproductive strategy of planktonic foraminifera, key pelagic calcifiers, has long remained elusive, hampering efforts to understand and model their population dynamics. This is particularly critical in polar oceans where their success relies on rapid population growth after the polar night. Here, we provide field and laboratory observations constraining the reproductive cycle of the dominant polar species Neogloboquadrina pachyderma in Antarctic and Arctic waters. We observe that asexual reproduction is a rare but persistent element of the reproductive strategy and that it is reflected in a dimorphism in proloculus and in the ratio of shell size versus the number of chambers between sexually and asexually produced individuals. This dimorphism in natural populations reveals that asexual reproduction supplies more than 75% of adult individuals. This indicates a multigenerational reproduction strategy, where the majority of the population releases gametes to facilitate recombination, while a minority persistently reproduces asexually, allowing rapid population growth as a prerequisite for success in the polar oceans.
Calanus helgolandicus - more than a guest in the north?
Authors: Schultz Mads , Choquet Marvin , Tverberg Vigdis , Hoarau Galice
Published: December 2022

Molecular identification of Calanus helgolandicus has revealed a more northern distribution for this boreal species than previously reported. We investigated an Arctic fjord to determine if local reproduction is taking place. Combining time series data from depth stratified sampling with molecular tools for species identification, we found C. helgolandicus from all stages throughout the year including males and females as well as a nauplius. These findings constitute strong evidence that C. helgolandicus is reproducing north of the Arctic Circle and their role in the ecosystem should be investigated further.
Information maximization explains state-dependent synaptic plasticity and memory reorganization during non-rapid eye movement sleep
Authors: Yoshida Kensuke , Toyoizumi Taro
Published: December 2022

Slow waves during the non-rapid eye movement (NREM) sleep reflect the alternating up and down states of cortical neurons; global and local slow waves promote memory consolidation and forgetting, respectively. Furthermore, distinct spike-timing-dependent plasticity (STDP) operates in these up and down states. The contribution of different plasticity rules to neural information coding and memory reorganization remains unknown. Here, we show that optimal synaptic plasticity for information maximization in a cortical neuron model provides a unified explanation for these phenomena. The model indicates that the optimal synaptic plasticity is biased toward depression as the baseline firing rate increases. This property explains the distinct STDP observed in the up and down states. Furthermore, it explains how global and local slow waves predominantly potentiate and depress synapses, respectively, if the background firing rate of excitatory neurons declines with the spatial scale of waves as the model predicts. The model provides a unifying account of the role of NREM sleep, bridging neural information coding, synaptic plasticity, and memory reorganization.
Detection of the 4.4-MeV gamma rays from 16O(ν, ν′)16O(12.97 MeV, 2−) with a water Cherenkov detector in supernova neutrino bursts
Authors: Sakuda Makoto , Suzuki Toshio , Reen Mandeep Singh , Nakazato Ken’ichiro , Suzuki Hideyuki
Published: December 2022

We first discuss and determine the isospin mixing of the two 2− states (12.53 MeV and 12.97 MeV) of the16O nucleus using inelastic electron scattering data. We then evaluate the cross section of 4.4-MeV γ rays produced in the neutrino neutral-current (NC) reaction 16O(ν, ν′)16O(12.97 MeV, 2−) in a water Cherenkov detector at a low energy, below 100 MeV. The detection of γ rays for Eγ > 5 MeV from the NC reaction 16O(ν, ν′)16O(Ex > 16 MeV, T = 1) with a water Cherenkov detector in supernova neutrino bursts has been proposed and discussed by several authors previously. In this article, we discuss a new NC reaction channel from 16O(12.97 MeV, 2−) producing a 4.4-MeV γ ray, the cross section of which is more robust and even larger at low energy (Eν < 25 MeV) than the NC cross section from 16O(Ex > 16 MeV, T = 1). We also evaluate the number of such events induced by neutrinos from supernova explosion which can be observed by the Super-Kamiokande, an Earth-based 32-kton water Cherenkov detector.
Outcomes of LGBTQ culturally sensitive training among civilian and military healthcare personnel
Authors: Oblea Pedro N , Bathan Nicole Q , Gaa Christyn A , Lustik Michael B , Tartavoulle Todd M , Nguyen-Wu Elizabeth D , Siaki Leilani A
Published: December 2022

Background

Lesbian, gay, bisexual, transgender, or queer (LGBTQ) military servicemembers are at higher risk of developing health problems compared to heterosexual peers. To improve outcomes and address negative attitudes, previous literature has recommended education of healthcare personnel. The purpose of our study was to evaluate the knowledge and skill outcomes of an LGBTQ cultural sensitivity training program.

Methods

We used a pretest/posttest design. Participants completed the Ally Identity Measure (AIM) to assess three subscales: knowledge and skills, openness and support, and oppression awareness. Participants included both military and civilian healthcare personnel from multiple disciplines. Descriptive statistics and pairwise analyses were used.

Results

A total of 101 participants answered both pretest and posttest. Across all AIM subscales, posttest scores demonstrated statistically significant (P < 0.001) increases from mean pretest scores. Completion rates for the pretest and posttest were 99% and 93%, respectively. The majority of participants were female (75%) and non-Hispanic (87%), composed of Caucasians (39%) and Asians (33%). Over one-third (39%) of participants were aged 30–39. Fifty percent were active-duty military and more than half (58%) of all participants did not have prior training in LGBTQ patient care. Statistically significant differences were found between the pretest and posttest scores for the knowledge and skills subscale (M = 2.64–3.70). The most significant increases were observed in Item 12 and Item 15 (M = 2.72–3.70) regarding awareness of theories and skill development to provide proper support, respectively.

Conclusion

These significant findings contribute to the currently limited research exploring LGBTQ cultural sensitivity training in both civilian and military settings. To our knowledge, this is the first time a cultural sensitivity training of this depth has been provided to active-duty servicemembers. Further research and development of similar educational programs integrating interactive participation can potentially aid in the delivery of improved care and military readiness for all servicemembers.
Location, location, location: does providing public health services from community pharmacies contribute to tackling health inequalities?
Authors: Evans Andrew , Mantzourani Efi , Gillespie David , Hughes Louise , Sharpe Georgia , Yip Nicola
Published: December 2022

Background

Community pharmacies have long been advocated as an accessible source of advice on health improvement in communities. This cross-sectional study explored the association between provision of pharmacy public health services and factors that might influence the extent to which pharmacies contribute to tackling inequalities.

Methods

Publically available data were used to explore the association between pharmacy public health service provision and pharmacy characteristics (socioeconomic deprivation, urbanity, opening hours and workload). Regression models were fitted to the number of service consultations. The association between the number of services provided and the mean number of consultations across each service was investigated using regression models.

Results

Pharmacies showed a propensity for being situated in areas of higher socioeconomic deprivation. There was no association between socioeconomic deprivation and number of service consultations a pharmacy provided. Clustering of pharmacies in less affluent areas led to over half of all public health service consultations being in the two most deprived quintiles.

Conclusions

Providing healthcare services from pharmacies in more deprived areas does not mean the public use them or that pharmacies will prioritize their delivery. The higher prevalence of pharmacies in disadvantaged communities is an important factor in ensuring pharmacy services support reducing inequalities.
The EU financial collateral directive: the distinguishing features of a security financial collateral arrangement?
Authors: Ezike Obiora
Published: December 2022

The first part of this article considers whether a system-neutral meaning of a title transfer financial collateral arrangement (TTFSA) can be identified in the EU Collateral Directive. This part looks at a similar issue—it considers whether system-neutral meaning of a security financial collateral arrangement (SFCA) can be identified in the Financial Collateral Arrangement Directive. It is argued that the definition of a SFCA in the Directive is based on the assumption that there is a specific organizing principle or concept that makes it easy to clearly identify, and demarcate, SFCAs from other types of security arrangements (particularly TTFCAs). While this assumption fits well within the model of Civil law systems, which may have a clear concept of ‘security right’, it does not fit in well within the common law. The arguments in this article call for a careful approach in the system-neutral definition of a SFCA in the Directive.
Learning the Drug-Target Interaction Lexicon
Authors: Singh Rohit , Sledzieski Samuel , Cowen Lenore , Berger Bonnie
Published: December 2022

Sequence-based prediction of drug-target interactions has the potential to accelerate drug discovery by complementing experimental screens. Such computational prediction needs to be generalizable and scalable while remaining sensitive to subtle variations in the inputs. However, current computational techniques fail to simultaneously meet these goals, often sacrificing performance on one to achieve the others. We develop a deep learning model, ConPLex, successfully leveraging the advances in pre-trained protein language models (“PLex”) and employing a novel protein-anchored contrastive co-embedding (“Con”) to outperform state-of-the-art approaches. ConPLex achieves high accuracy, broad adaptivity to unseen data, and specificity against decoy compounds. It makes predictions of binding based on the distance between learned representations, enabling predictions at the scale of massive compound libraries and the human proteome. Furthermore, ConPLex is interpretable, which enables us to visualize the drug-target lexicon and use embeddings to characterize the function of human cell-surface proteins. We anticipate ConPLex will facilitate novel drug discovery by making highly sensitive and interpretable in-silico drug screening feasible at genome scale. Con-PLex is available open-source athttps://github.com/samsledje/ConPLex.

Significance Statement

In time and money, one of the most expensive steps of the drug discovery pipeline is the experimental screening of small molecules to see which will bind to a protein target of interest. Therefore, accurate high-throughput computational prediction of drug-target interactions would unlock significant value, guiding and prioritizing promising candidates for experimental screening. We introduce ConPLex, a machine learning method for predicting drug-target binding which achieves state-of-the-art accuracy on many types of targets by using a pre-trained protein language model. The approach co-locates the proteins and the potential drug molecules in a shared feature space while learning to contrast true drugs from similar non-binding “decoy” molecules. ConPLex is extremely fast, which allows it to rapidly shortlist candidates for deeper investigation.
Plasma protein biomarkers predict both the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity: the TEDDY Study
Authors: Nakayasu Ernesto S. , Bramer Lisa M. , Ansong Charles , Schepmoes Athena A. , Fillmore Thomas L. , Gritsenko Marina A. , Clauss Therese R. , Gao Yuqian , Piehowski Paul D. , Stanfill Bryan A. , Engel Dave W. , Orton Daniel J. , Moore Ronald J. , Qian Wei-Jun , Sechi Salvatore , Frohnert Brigitte I. , Toppari Jorma , Ziegler Anette-G. , Lernmark Åke , Hagopian William , Akolkar Beena , Smith Richard D. , Rewers Marian J. , Webb-Robertson Bobbie-Jo M. , Metz Thomas O.
Published: December 2022

Type 1 diabetes (T1D) results from an autoimmune destruction of pancreatic β cells. A significant gap in understanding the disease cause is the lack of predictive biomarkers for each of its developmental stages. Here, we conducted a blinded, two-phase case-control plasma proteomics analysis of children enrolled in the TEDDY study to identify biomarkers predictive of autoimmunity and T1D development. First, we performed untargeted proteomics analyses of 2,252 samples from 184 individuals and identified 376 regulated proteins. Complement/coagulation, inflammatory signaling and metabolic proteins were regulated even prior to autoimmunity onset. Extracellular matrix proteins and antigen presentation were differentially regulated in individuals with autoimmunity who progressed to T1D versus those who maintained normoglycemia. We then performed targeted proteomics measurements of 167 proteins in 6,426 samples from 990 individuals and validated 83 biomarkers. A machine learning analysis predicted both the development of persistent autoantibodies and T1D onset 6 months before autoimmunity initiation, with an area under the receiver operating characteristic curve of 0.871 and 0.918, respectively. Our study identified and validated biomarkers highlighting pathways affected in different stages of T1D development.
Composition efficacy of Unsaturated Arachidonic acid, Diterpenoids, Malvin (C29H35ClO17), and Bergenin to neutralise venom from different venomous snake species
Authors: Al-Tobi Lujaina N. H. , Albusaidi Juma.Z.K , Ajabri Ali.A , Idris Mohammed A. , Hasson Sidgi S. A A.
Published: December 2022

Snakebite envenomation is a serious problem in tropical and subtropical countries. Antivenom is the only treatment used to treat snake envenomation, however it is unable to neutralise local haemorrhage. Therefore, this study’s aim is to evaluate the efficacy ofP. dulceleaf extract to neutralise local haemorrhage induced by three clinically important snake species,B. jararaca, C. atroxandE. carinatus. Moreover, to determine the active components which are responsible for this activity. The plant leaves were extracted using different solvents, however, only E/e extract showed the best neutralizing capacity. The increasing doses, DF-1:2; 1:4, of E/e extract allowed better neutralizing ability s.c. In contrast, the oral/ i.p. acute toxicity test revealed that the optimal doses for the administration of E/e were 1 and 8 mg/kg. In addition to that, E/e was tested for its anti-lathality of LD50usingB. jararacavenom (1.1mg/kg) i.p., where the higher doses of 16 and 24 mg/kg killed 75% of BALB/C mice. Consequently, the different components of E/e extract were isolated with HPLC. The different components were grouped and tested to uncover the active ones. The results revealed that only three fractions were active, Frc11, Frc13, and Frc14. The active fractions showed a disparity in neutralizing the individual venoms, however, the best neutralising capacity was scored for Frc11. When the same fractions were pooled together, they showed a complete neutralizing ability against individual venoms as well as the pooled venoms. That was confirmed with the anti-gelatinase activity test, where pooled fraction inhibited the SVMP enzyme which is responsible for gelatinase activity. The phytochemical characterisation showed that the active fractions consist mainly of secondary metabolites such as tannins and polyphenols. MALDI-TOF MS confirmed the presence of secondary metabolites in the active fractions. The same fractions were tested for their anti-lethal activity using the pooled venoms (LD100), the results were statistically not significant, as all mice died including the positive controls. Nevertheless, the active fractions showed a noticeable increasing in survival time period especially Frc13 with an average survival time of 37 minutes. The positive control, IAV, scored the longest survival period with a gap of 11 minutes from Frc13.
A framework for deriving analytic long-term behavior of biochemical reaction networks
Authors: Hernandez Bryan S. , Lubenia Patrick Vincent N. , Johnston Matthew D. , Kim Jae Kyoung
Published: December 2022

The long-term behaviors of biochemical systems are described by their steady states. Deriving these states directly for complex networks arising from real-world applications, however, is often challenging. Recent work has consequently focused on network-based approaches. Specifically, biochemical reaction networks are transformed into weakly reversible and deficiency zero networks, which allows the derivation of their analytic steady states. Identifying this transformation, however, can be challenging for large and complex networks. In this paper, we address this difficulty by breaking the complex network into smaller independent subnetworks and then transforming the subnetworks to derive the analytic steady states of each subnetwork. We show that stitching these solutions together leads to the the analytic steady states of the original network. To facilitate this process, we develop a user-friendly and publicly available package, COMPILES (COMPutIng anaLytic stEady States). With COMPILES, we can easily test the presence of bistability of a CRISPRi toggle switch model, which was previously investigated via tremendous number of numerical simulations and within a limited range of parameters. Furthermore, COMPILES can be used to identify absolute concentration robustness (ACR), the property of a system that maintains the concentration of particular species at a steady state regardless of any initial concentrations. Specifically, our approach completely identifies all the species with and without ACR in a complex insulin model. Our method provides an effective approach to analyzing and understanding complex biochemical systems.

Author summary

Steady states describe the long-term behaviors of biochemical systems, which are typically based on ordinary differential equations. To derive a steady state analytically, significant attention has been given in recent years to network-based approaches. While this approach allows a steady state to be derived as long as a network has a special structure, complex and large networks rarely have this structural property. We address this difficulty by breaking the network into smaller and more manageable independent subnetworks, and then use the network-based approach to derive the analytic steady state of each subnetwork. Stitching these solutions together allows us to derive the analytic steady state of the original network. To facilitate this process, we develop a user-friendly and publicly available package, COMPILES. COMPILES identifies critical biochemical properties such as the presence of bistability in a genetic toggle switch model and absolute concentration robustness in a complex insulin signaling pathway model.
TLS2trees: a scalable tree segmentation pipeline for TLS data
Authors: Wilkes Phil , Disney Mathias , Armston John , Bartholomeus Harm , Bentley Lisa , Brede Benjamin , Burt Andrew , Calders Kim , Chavana-Bryant Cecilia , Clewley Daniel , Duncanson Laura , Forbes Brieanne , Krisanski Sean , Malhi Yadvinder , Moffat David , Origo Niall , Shenkin Alexander , Yang Wanxin
Published: December 2022

Above Ground Biomass (AGB) is an important metric used to quantify the mass of carbon stored in terrestrial ecosystems. For forests, this is routinely estimated at the plot scale (typically ≥1 ha) using inventory measurements and allometry. In recent years, Terrestrial Laser Scanning (TLS) has appeared as a disruptive technology that can generate a more accurate assessment of tree and plot scale AGB; however, operationalising TLS methods has had to overcome a number of challenges. One such challenge is the segmentation of individual trees from plot level point clouds that are required to estimate woody volume, this is often done manually (e.g. with interactive point cloud editing software) and can be very time consuming. Here we presentTLS2trees, an automated processing pipeline and set of Python command line tools that aims to redress this processing bottleneck.TLS2treesconsists of existing and new methods and is specifically designed to be horizontally scalable. The processing pipeline is demonstrated across 10 plots of 7 forest types; from open savanna to dense tropical rainforest, where a total of 10,557 trees are segmented.TLS2treessegmented trees are compared to 1,281 manually segmented trees. Results indicate thatTLS2treesperforms well, particularly for larger trees (i.e. the cohort of largest trees that comprise 50% of total plot volume), where plot-wise tree volume bias is ±0.4 m3and %RMSE is~60%. To facilitate improvements to the presented methods as well as modification for other laser scanning modes (e.g. mobile and UAV laser scanning),TLS2treesis a free and open-source software (FOSS).