bluuebunny/crossref_metadata_2025 huggingface dataset:
Budget impact analysis of a pilot polypharmacy clinic
Authors: Bennett Frances , Barron Andrew , Shah Neha , Webb David J , Sofat Reecha
Published: April 2022

Background/Aims

Inappropriate polypharmacy can lead to adverse events and increased healthcare costs. This study estimated the budget impact of providing a specialist onward referral service for patients with potentially problematic polypharmacy.

Methods

A multidisciplinary team-led pilot polypharmacy clinic, dedicated to reviewing patients prescribed more than 10 different medications, was trialled in a secondary care setting. Potentially inappropriate prescribing was identified and addressed. Data from the pilot clinic regarding costs, direct savings and indirect savings were used to create budget impact models. Two service models were proposed: an outpatient model, based on the pilot clinic, and an integrated model, a theoretical integrated service collaborating with colleagues in primary care. Base case results and sensitivity analyses were calculated for both models.

Results

Annual overall cost savings from the outpatient model and integrated model were estimated at £67 158 and £34 176 respectively. Both models were predicted to produce both direct and indirect savings from stopping unnecessary drugs and preventing hospital admissions for adverse drug reactions. Sensitivity analysis confirmed these results across all included variables except the number of medications stopped at review.

Conclusions

Specialist onward referral services, dedicated to reviewing complex patients with high-risk polypharmacy, could offer significant cost savings, while also preventing adverse side effects and drug-related events.
Will 2022 be the year that ‘integrates’ health and social care in England?
Authors: Groen Bernard
Published: April 2022

With the Health and Care Bill 2022 scheduled to come into force in July, Bernard Groen discusses the transition to integrated care systems and what is likely to be required of their leaders.
Wellbeing in primary care: the reality
Authors: Rollings Caroline
Published: April 2022

Caroline Rollings, wellbeing lead for the National Association of Primary Care and joint chair of the One Voice Group, shares her insight into the immense pressure facing NHS primary care services, the consequences of that pressure, and strategies that managers can use to help their colleagues to cope.
Minimalistic fully convolution networks (MFCN): pixel-level classification for hyperspectral image with few labeled samples
Authors: Xu Buyun , Hou Weijun , Wei Yiwei , Wang Yiting , Li Xihai
Published: April 2022

Most of the existing deep learning methods for hyperspectral image (HSI) classification use pixel-wise or patch-wise classification. In this paper, we propose an image-wise classification method, where the network input is the original hyperspectral cube rather than the spectral curve of each pixel (i.e., pixel-wise) or neighbor region of each pixel (i.e., patch-wise). Specifically, we propose a minimalistic fully convolution network (MFCN) and a semi-supervised loss function, which can perform pixel-level classification for HSI with few labeled samples. The comparison experiments demonstrated the progress of our methods, using three new benchmark HSI datasets (WHU-Hi-LongKou, WHU-Hi-HanChuan and WHU-Hi-HongHu) with wavelength range from 400 to 1000nm. In the comparison experiments, we randomly selected 25 labeled pixels from each class for training, equivalent to only 0.11%, 0.16%, and 0.14% of all labeled pixels for the three datasets, respectively. In addition, through ablation studies and theoretical analysis, we verified and analyzed the effectiveness and superiority of our design choices.
Direct modulation bandwidth enhancement of uncooled DFB laser operating over a wide temperature range based on groove-in-trench waveguide structure
Authors: Han Yu , Tian Qi , Yang Sikang , Luan Jing , Zhang Ruigang , He Pengxiang , Liu Deming , Zhang Minming
Published: April 2022

Uncooled direct modulation DFB laser offers high speed transmission rate over a wide temperature range with high reliability and low cost, making it a cost-effective light source choice for 5G fronthaul and data center applications. However, a significant 3dB bandwidth decrease can be observed in high temperature for conventional DFB lasers. We present an uncooled DFB laser operating up to 85°C with extended direct modulation bandwidth and high reliability based on a novel groove-in-trench ridge waveguide structure, where two narrow grooves penetrating the active layer are etched symmetrically in the two conventional trenches by deep wet etching, respectively. By optimizing the distance between the groove and the mesa stripe, we obtain a 3dB bandwidth of 15.3 GHz at 85°C, which is a 3.7 GHz improvement compared with the conventional ridge waveguide DFB laser. Transmissions of 25 Gb/s NRZ signal at 25°C and 85°C with clear eye openings have been demonstrated. It also achieves 25 Gb/s transmission over 10 km optical fiber with a low power penalty of 0.5 dB for a bit error rate of 10−12 at 85°C. In addition, the result of 2000-hour aging test shows that the proposed groove-in-trench structure DFB lasers have the same excellent reliability as the conventional ones.
Phylogenetic profiling in eukaryotes: The effect of species, orthologous group, and interactome selection on protein interaction prediction
Authors: Deutekom Eva S. , van Dam Teunis J. P. , Snel Berend
Published: April 2022

Phylogenetic profiling in eukaryotes is of continued interest to study and predict the functional relationships between proteins. This interest is likely driven by the increased number of available diverse genomes and computational methods to infer orthologies. The evaluation of phylogenetic profiles has mainly focussed on reference genome selection in prokaryotes. However, it has been proven to be challenging to obtain high prediction accuracies in eukaryotes. As part of our recent comparison of orthology inference methods for eukaryotic genomes, we observed a surprisingly high performance for predicting interacting orthologous groups. This high performance, in turn, prompted the question of what factors influence the success of phylogenetic profiling when applied to eukaryotic genomes. Here we analyse the effect of species, orthologous group and interactome selection on protein interaction prediction using phylogenetic profiles. We select species based on the diversity and quality of the genomes and compare this supervised selection with randomly generated genome subsets. We also analyse the effect on the performance of orthologous groups defined to be in the last eukaryotic common ancestor of eukaryotes to that of orthologous groups that are not. Finally, we consider the effects of reference interactome set filtering and reference interactome species. In agreement with other studies, we find an effect of genome selection based on quality, less of an effect based on genome diversity, but a more notable effect based on the amount of information contained within the genomes. Most importantly, we find it is not merely selecting the correct genomes that is important for high prediction performance. Other choices in meta parameters such as orthologous group selection, the reference species of the interaction set, and the quality of the interaction set have a much larger impact on the performance when predicting protein interactions using phylogenetic profiles. These findings shed light on the differences in reported performance amongst phylogenetic profiles approaches, and reveal on a more fundamental level for which types of protein interactions this method has most promise when applied to eukaryotes.
Two fingerprinting sets for Humulus lupulus based on KASP and microsatellite markers
Authors: Driskill Mandie , Pardee Katie , Hummer Kim E. , Zurn Jason D. , Amundsen Keenan , Wiles Annette , Wiedow Claudia , Patzak Josef , Henning John A. , Bassil Nahla V.
Published: April 2022

Verification of clonal identity of hop (Humulus lupulusL.) cultivars within breeding programs and germplasm collections is vital to conserving genetic resources. Accurate and economic DNA-based tools are needed in dioecious hop to confirm identity and parentage, neither of which can be reliably determined from morphological observations. In this study, we developed two fingerprinting sets for hop: a 9-SSR fingerprinting set containing high-core repeats that can be run in a single PCR reaction and a kompetitive allele specific PCR (KASP) assay of 25 single nucleotide polymorphisms (SNPs). The SSR set contains a sex-linked primer pair, HI-AGA7, that was used to genotype 629 hop accessions from the US Department of Agriculture (USDA) National Clonal Germplasm Repository (NCGR), the USDA Forage Seed and Cereal Research (FSCR), and the University of Nebraska-Lincoln (UNL) collections. The SSR set identified unique genotypes except for 89 sets of synonymous samples. These synonyms included: cultivars with different designations, the same cultivars from different sources, heat-treated clones, and clonal variants. Population structure analysis clustered accessions into wild North American (WNA) and cultivated groups. Diversity was slightly higher in the cultivated samples due to larger sample size. Parentage and sib-ship analyses were used to identify true-to-type cultivars. The HI-AGA7 marker generated two male- and nine female-specific alleles among the cultivated and WNA samples. The SSR and KASP fingerprinting sets were compared in 190 samples consisting of cultivated and WNA accession for their ability to confirm identity and assess diversity and population structure. The SSR fingerprinting set distinguished cultivars, selections and WNA accessions while the KASP assays were unable to distinguish the WNA samples and had lower diversity estimates than the SSR set. Both fingerprinting sets are valuable tools for identity confirmation and parentage analysis in hop for different purposes. The 9-SSR assay is cost efficient when genotyping a small number of wild and cultivated hop samples (<96) while the KASP assay is easy to interpret and cost efficient for genotyping a large number of cultivated samples (multiples of 96).
Feasibility and preliminary efficacy for morning bright light therapy to improve sleep and plasma biomarkers in US Veterans with TBI. A prospective, open-label, single-arm trial
Authors: Elliott Jonathan E. , McBride Alisha A. , Balba Nadir M. , Thomas Stanley V. , Pattinson Cassandra L. , Morasco Benjamin J. , Wilkerson Andrea , Gill Jessica M. , Lim Miranda M.
Published: April 2022

Mild traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes including mood, pain, and quality of life. Present therapies to treat sleep-wake disturbances in those with TBI (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Thus, this study aimed to assess the feasibility and preliminary efficacy of morning bright light therapy, to improve sleep in Veterans with TBI (NCT03578003). Thirty-three Veterans with history of TBI were prospectively enrolled in a single-arm, open-label intervention using a lightbox (~10,000 lux at the eye) for 60-minutes every morning for 4-weeks. Pre- and post-intervention outcomes included questionnaires related to sleep, mood, TBI, post-traumatic stress disorder (PTSD), and pain; wrist actigraphy as a proxy for objective sleep; and blood-based biomarkers related to TBI/sleep. The protocol was rated favorably by ~75% of participants, with adherence to the lightbox and actigraphy being ~87% and 97%, respectively. Post-intervention improvements were observed in self-reported symptoms related to insomnia, mood, and pain; actigraphy-derived measures of sleep; and blood-based biomarkers related to peripheral inflammatory balance. The severity of comorbid PTSD was a significant positive predictor of response to treatment. Morning bright light therapy is a feasible and acceptable intervention that shows preliminary efficacy to treat disrupted sleep in Veterans with TBI. A full-scale randomized, placebo-controlled study with longitudinal follow-up is warranted to assess the efficacy of morning bright light therapy to improve sleep, biomarkers, and other TBI related symptoms.
Estimating the effects of lockdown timing on COVID-19 cases and deaths in England: A counterfactual modelling study
Authors: Arnold Kellyn F. , Gilthorpe Mark S. , Alwan Nisreen A. , Heppenstall Alison J. , Tomova Georgia D. , McKee Martin , Tennant Peter W. G.
Published: April 2022

Background

During the first wave of the COVID-19 pandemic, the United Kingdom experienced one of the highest per-capita death tolls worldwide. It is debated whether this may partly be explained by the relatively late initiation of voluntary social distancing and mandatory lockdown measures. In this study, we used simulations to estimate the number of cases and deaths that would have occurred in England by 1 June 2020 if these interventions had been implemented one or two weeks earlier, and the impact on the required duration of lockdown.

Methods

Using official reported data on the number of Pillar 1 lab-confirmed cases of COVID-19 and associated deaths occurring in England from 3 March to 1 June, we modelled: the natural (i.e. observed) growth of cases, and the counterfactual (i.e. hypothetical) growth of cases that would have occurred had measures been implemented one or two weeks earlier. Under each counterfactual condition, we estimated the expected number of deaths and the time required to reach the incidence observed under natural growth on 1 June.

Results

Introducing measures one week earlier would have reduced by 74% the number of confirmed COVID-19 cases in England by 1 June, resulting in approximately 21,000 fewer hospital deaths and 34,000 fewer total deaths; the required time spent in full lockdown could also have been halved, from 69 to 35 days. Acting two weeks earlier would have reduced cases by 93%, resulting in between 26,000 and 43,000 fewer deaths.

Conclusions

Our modelling supports the claim that the relatively late introduction of social distancing and lockdown measures likely increased the scale, severity, and duration of the first wave of COVID-19 in England. Our results highlight the importance of acting swiftly to minimise the spread of an infectious disease when case numbers are increasing exponentially.
Cross-disorder and disorder-specific deficits in social functioning among schizophrenia and alzheimer’s disease patients
Authors: Saris Ilja M. J. , Aghajani Moji , Jongs Niels , Reus Lianne M. , van der Wee Nic J. A. , Bilderbeck Amy C. , Winter van Rossum Inge , Arango Celso , de la Torre-Luque Alejandro , Malik Asad , Raslescu Andreea , Dawson Gerard R. , Ayuso-Mateos José L. , Kas Martien J. , Penninx Brenda W. J. H.
Published: April 2022

Background

Social functioning is often impaired in schizophrenia (SZ) and Alzheimer’s disease (AD). However, commonalities and differences in social dysfunction among these patient groups remain elusive.

Materials and methods

Using data from the PRISM study, behavioral (all subscales and total score of the Social Functioning Scale) and affective (perceived social disability and loneliness) indicators of social functioning were measured in patients with SZ (N = 56), probable AD (N = 50) and age-matched healthy controls groups (HC, N = 29 and N = 28). We examined to what extent social functioning differed between disease and age-matched HC groups, as well as between patient groups. Furthermore, we examined how severity of disease and mood were correlated with social functioning, irrespective of diagnosis.

Results

As compared to HC, both behavioral and affective social functioning seemed impaired in SZ patients (Cohen’s d’s 0.81–1.69), whereas AD patients mainly showed impaired behavioral social function (Cohen’s d’s 0.65–1.14). While behavioral indices of social functioning were similar across patient groups, SZ patients reported more perceived social disability than AD patients (Cohen’s d’s 0.65). Across patient groups, positive mood, lower depression and anxiety levels were strong determinants of better social functioning (p’s <0.001), even more so than severity of disease.

Conclusions

AD and SZ patients both exhibit poor social functioning in comparison to age- and sex matched HC participants. Social dysfunction in SZ patients may be more severe than in AD patients, though this may be due to underreporting by AD patients. Across patients, social functioning appeared as more influenced by mood states than by severity of disease.
Margin between success and failure of PDA stenting for duct-dependent pulmonary circulation
Authors: Agha Hala Mounir , Abd -El Aziz Osama , Kamel Ola , Sheta Sahar S. , El-Sisi Amal , El-Saiedi Sonia , Fatouh Aya , Esmat Amira , Abdelmohsen Gaser , Hanna Baher , Hussien Mai , Sobhy Rodina
Published: April 2022

Objectives

Percutaneous patent ductus arteriosus (PDA) stenting is a therapeutic modality in patients with duct-dependent pulmonary circulation with reported success rates from 80–100%. The current study aims to assess the outcome and the indicators of success for PDA stenting in different ductal morphologies using various approaches.

Methods

A prospective cohort study from a single tertiary center presented from January 2018 to December 2019 that included 96 consecutive infants with ductal-dependent pulmonary circulation and palliated with PDA stenting. Patients were divided according to PDA origin into 4 groups: Group 1: PDA from proximal descending aorta, Group 2: from undersurface of aortic arch, Group 3: opposite the subclavian artery, Group 4: opposite the innominate/brachiocephalic artery.

Results

The median age of patients was 22 days and median weight was 3 kg. The procedure was successful in 78 patients (81.25%). PDA was tortuous in 70 out of 96 patients. Femoral artery was the preferred approach in Group 1 (63/67), while axillary artery access was preferred in the other groups (6/11 in Group 2, 11/17 in Group 3, 1/1 in Group 4, P <0.0001). The main cause of procedural failure was inadequate parked coronary wire inside one of the branch of pulmonary arteries (14 cases; 77.7%), while 2 cases (11.1%) were complicated by acute stent thrombosis, and another 2 cases with stent dislodgment. Other procedural complications comprised femoral artery thrombosis in 7 cases (7.2%). Patients with straight PDA, younger age at procedure and who had larger PDA at pulmonary end had higher odds for success (OR = 8.01, 2.94, 7.40, CI = 1.011–63.68, 0.960–0.99, 1.172–7.40,respectively, P = 0.048, 0.031,0.022 respectively).

Conclusions

The approach for PDA stenting and hence the outcome is markedly determined by the PDA origin and morphology. Patients with straight PDA, younger age at procedure and those who had relatively larger PDA at the pulmonary end had better opportunity for successful procedure.
Seed priming with growth regulators modulates production, physiology and antioxidant defense of Indian squash (Praecitrullus fistulosus) under semi-arid conditions
Authors: Qamar Rafi , Khan Sanaullah , Safdar Muhammad Ehsan , Atique-ur-Rehman  , Rehman Abdul , Javeed Hafiz Muhammad Rashad , Nadeem Muhammad Ather , Al-Yahyai Rashid , Alkahtani Jawaher
Published: April 2022

Indian squash (Praecitrullus fistulosus) crop faces heat and drought during its growth that is considered the most important abiotic stress in semi-arid areas. Seed priming with growth regulators enhances stress tolerance; hence, mitigates the adverse effects of unpredictable stresses due to adverse weather conditions. This two-year (2019 and 2020) study was conducted to infer the role of seed priming in improving heat tolerance of Indian squash (cultivar Sahavi) through improvement in physiological and antioxidant defense systems. Six treatments that included no priming (control), hydropriming, priming with indole acetic acid (IAA) at 100 mg L-1, salicylic acid (SA) at 50 mg L-1, ascorbic acid (AA) at 100 mg L-1 and thiourea at 500 mg L-1 each for 06 hours) were included in the study. Results revealed that priming with AA and SA significantly (P ≤ 0.05) enhanced germination (39 and 47%), germination index (57 and 58%), plant height (23 and 22%), vine length (15 and 14%), number of fruits per plant (62%), fruit weight per plant (66 and 67%), economic yield (32%), photosynthesis rate (18 and 17%), protein content (10%), proline (23%), glycine betaine (3%), malondialdehyde content (11 and 10%) and catalase activity (24%) compared to control treatment. Furthermore, seed priming with AA and SA significantly (P ≤ 0.05) shortened the mean germination time (25 and 28%) compared to the control. The results indicated that AA and SA had significant potential to mitigate adverse effects of heat stress in Indian squash. Findings from this study showed that seed priming with AA and SA promoted heat-stress tolerance and enhanced growth and productivity of Indian squash.
DNA barcoding reveals global and local influences on patterns of mislabeling and substitution in the trade of fish in Mexico
Authors: Munguia-Vega Adrian , Terrazas-Tapia Renata , Dominguez-Contreras Jose F. , Reyna-Fabian Mariana , Zapata-Morales Pedro
Published: April 2022

Mislabeling of seafood is a global phenomenon that can misrepresent the status and level of consumption of wild fish stocks while concealing the use of many other wild species or those originating from aquaculture and sold as substitutes. We conducted a DNA barcoding study in three cities within Mexico (Mazatlan, Mexico City and Cancun) and sequenced the COI gene in 376 fish samples sold as 48 distinct commercial names at fish markets, grocery stores, and restaurants. Our goal was to identify the main species sold, their mislabeling rates and the species most used as substitutes. Overall, the study-wide mislabeling rate was 30.8% (95% CI 26.4–35.6). Half of the samples collected belonged to five species traded globally (yellowfin tuna, Atlantic salmon, mahi, swai, and tilapia), most of them with important aquaculture or ranching production levels. These species were commonly used as substitutes for other species and showed low mislabeling rates themselves (≤ 11%, except mahi mahi with 39% mislabeling). The other half of the samples revealed nearly 100 species targeted by small-scale fishers in Mexico and sold under 42 distinct commercial names. Popular local commercial names (dorado, marlin, mero, robalo, mojarra, huachinango, pargo, sierra) showed the highest mislabeling rates (36.3% to 94.4%) and served to sell many of the 53 species identified as substitutes in our study. We discuss the observed patterns in relation to landing and import data showing differences in availability of commercial species and the links to explain observed mislabeling rates and the use of a species as a substitute for other species. We also outline some of the implications of establishing a labeling and traceability standard as an alternative to improve transparency in the trade of seafood products in Mexico.
A novel computational strategy for defining the minimal protein molecular surface representation
Authors: Grassmann Greta , Miotto Mattia , Di Rienzo Lorenzo , Gosti Giorgio , Ruocco Giancarlo , Milanetti Edoardo
Published: April 2022

Most proteins perform their biological function by interacting with one or more molecular partners. In this respect, characterizing local features of the molecular surface, that can potentially be involved in the interaction with other molecules, represents a step forward in the investigation of the mechanisms of recognition and binding between molecules. Predictive methods often rely on extensive samplings of molecular patches with the aim to identify hot spots on the surface. In this framework, analysis of large proteins and/or many molecular dynamics frames is often unfeasible due to the high computational cost. Thus, finding optimal ways to reduce the number of points to be sampled maintaining the biological information (including the surface shape) carried by the molecular surface is pivotal. In this perspective, we here present a new theoretical and computational algorithm with the aim of defining a set of molecular surfaces composed of points not uniformly distributed in space, in such a way as to maximize the information of the overall shape of the molecule by minimizing the number of total points. We test our procedure’s ability in recognizing hot-spots by describing the local shape properties of portions of molecular surfaces through a recently developed method based on the formalism of 2D Zernike polynomials. The results of this work show the ability of the proposed algorithm to preserve the key information of the molecular surface using a reduced number of points compared to the complete surface, where all points of the surface are used for the description. In fact, the methodology shows a significant gain of the information stored in the sampling procedure compared to uniform random sampling.
Cryo-ET detects bundled triple helices but not ladders in meiotic budding yeast
Authors: Ma Olivia X. , Chong Wen Guan , Lee Joy K. E. , Cai Shujun , Siebert C. Alistair , Howe Andrew , Zhang Peijun , Shi Jian , Surana Uttam , Gan Lu
Published: April 2022

In meiosis, cells undergo two sequential rounds of cell division, termed meiosis I and meiosis II. Textbook models of the meiosis I substage called pachytene show that nuclei have conspicuous 100-nm-wide, ladder-like synaptonemal complexes and ordered chromatin loops. It remains unknown if these cells have any other large, meiosis-related intranuclear structures. Here we present cryo-ET analysis of frozen-hydrated budding yeast cells before, during, and after pachytene. We found no cryo-ET densities that resemble dense ladder-like structures or ordered chromatin loops. Instead, we found large numbers of 12-nm-wide triple-helices that pack into ordered bundles. These structures, herein called meiotic triple helices (MTHs), are present in meiotic cells, but not in interphase cells. MTHs are enriched in the nucleus but not enriched in the cytoplasm. Bundles of MTHs form at the same timeframe as synaptonemal complexes (SCs) in wild-type cells and in mutant cells that are unable to form SCs. These results suggest that in yeast, SCs coexist with previously unreported large, ordered assemblies.
Inhibitory potentials of Streptomyces exfoliatus strain ‘MUJA10’ against bacterial pathogens isolated from rural areas in Riyadh, Saudi Arabia
Authors: Alahadeb Jawaher Ibrahim
Published: April 2022

Healthcare-associated infections are resulting in human morbidity and mortality worldwide. These infections are directly proportional to increased multidrug resistance (MDR), which limits antibiotic treatment and make the treatment of infections challenging. Streptomyces spp. are well known to produce various biologically active compounds. Therefore, these are considered as promising biological control agents against wide range of bacterial pathogens. This study was conducted to isolate and identify the most efficient antibiotic-producing Streptomyces St 45 isolate against Staphylococcus aureus ATCC29737, Salmonella typhimurium ATCC25566, E. coli 0157h7 ATCC25922 and Bacillus subtilis. A total 40 soil and 10 water (from wells) samples were processed using standard microbiological techniques at King Faisal Research Centre, Riyadh, Saudi Arabia. The selected Streptomyces St 45 isolate was grown to produce biologically active metabolites, and the minimum concentration (MIC) was determined. Sixty isolates with antibacterial properties were selected. The 16s rRNA gene analysis was used to identify the strongest Streptomyces St 45 strain. The highest zone of inhibition (ZOI) was provided by ‘MUJA10’ strain of S. exfoliatus against Staphylococcus aureus ATCC29737 (51.33 ± 2.15 mm). The MIC value of ‘MUJA10’ metabolite of S. exfoliatus strain against Salmonella typhimurium ATCC25566 and E. coli 0157h7 ATCC25922 was 0.125 mg/ml. However, Bacillus subtilis had a MIC of 0.625 mg/ml and Staphylococcus aureus ATCC29737 had a MIC of 2.5 mg/ml. In conclusion, Streptomyces exfoliatus strain ‘MUJA10’ obtained from soil exhibited high inhibitory potential against human pathogens. The 16s rRNA gene analysis revealed that Streptomyces St 45 isolate was similar to Streptomyces exfoliatus A156.7 with 98% similarity and confirmed as Streptomyces exfoliates ‘MUJA10’ at gene bank with gene accession number OL720257.
Analysis of modular gene co-expression networks reveals molecular pathways underlying Alzheimer’s disease and progressive supranuclear palsy
Authors: Iohan Lukas da Cruz Carvalho , Lambert Jean-Charles , Costa Marcos R.
Published: April 2022

A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. Gene expression alterations in the diseased brain is a potential source of information about biological processes affected by pathology. In this work, we performed a systematic comparison of gene expression alterations in the brains of human patients diagnosed with Alzheimer’s disease (AD) or Progressive Supranuclear Palsy (PSP) and animal models of amyloidopathy and tauopathy. Using a systems biology approach to uncover biological processes associated with gene expression alterations, we could pinpoint processes more strongly associated with tauopathy/PSP and amyloidopathy/AD. We show that gene expression alterations related to immune-inflammatory responses preponderate in younger, whereas those associated to synaptic transmission are mainly observed in older AD patients. In PSP, however, changes associated with immune-inflammatory responses and synaptic transmission overlap. These two different patterns observed in AD and PSP brains are fairly recapitulated in animal models of amyloidopathy and tauopathy, respectively. Moreover, in AD, but not PSP or animal models, gene expression alterations related to RNA splicing are highly prevalent, whereas those associated with myelination are enriched both in AD and PSP, but not in animal models. Finally, we identify 12 AD and 4 PSP genetic risk factors in cell-type specific co-expression modules, thus contributing to unveil the possible role of these genes to pathogenesis. Altogether, this work contributes to unravel the potential biological processes affected by amyloid versus tau pathology and how they could contribute to the pathogenesis of AD and PSP.
Predictors of loss to follow-up from HIV antiretroviral therapy in Namibia
Authors: Hong Steven Y. , Winston Anna , Mutenda Nicholus , Hamunime Ndapewa , Roy Tuhin , Wanke Christine , Tang Alice M. , Jordan Michael R.
Published: April 2022

Despite progress on population-level HIV viral suppression, unknown outcomes amongst people who have initiated antiretroviral therapy (ART) in low- and middle-income countries, commonly referred to as loss to follow-up (LTFU), remains a barrier. The mean global estimate of LTFU is 20%, exceeding the World Health Organization target of <15%. Pervasive predictors associated with LTFU include younger age, low body mass index, low CD4 count, advanced HIV clinical stage and certain ART regimens. In Namibia, ART use by eligible individuals exceeds 85%, surpassing the global average. Nonetheless, LTFU remains a barrier to achieving viral suppression and requires research to elucidate context-specific factors. An observational cohort study was conducted in Namibia in 2012 by administering surveys to individuals who presented for HIV care and initiated ART for the first time. Additional data were collected from routine medical data monitoring systems. Participants classified as LTFU at 12 months were traced to confirm their status. Predictors of LTFU were analyzed using multivariable logistic regression. Of those who presented consecutively to initiate ART, 524 were identified as eligible to enroll in the study, 497 enrolled, and 474 completed the baseline questionnaire. The cohort had mean age 36 years, 39% were male, mean CD4 cell count 222 cells/mm3, 17% were WHO HIV clinical stage III-IV, and 14% started efavirenz-based regimens. Tracing participants classified as LTFU yielded a re-categorization from 27.8% (n = 132) to 14.3% (n = 68) LTFU. In the final multivariable model, factors associated with confirmed LTFU status were: younger age (OR 0.97, 95% CI 1.00–1.06, p = 0.02); male sex (OR 2.34, CI 1.34–4.06, p = 0.003); difficulty leaving work or home to attend clinic (OR 2.55, CI 1.40–4.65, p = 0.002); and baseline efavirenz-based regimen (OR 2.35, CI 1.22–4.51, p = 0.01). Interventions to reduce LTFU should therefore target young men, particularly those who report difficulty leaving work or home to attend clinic and are on an efavirenz-based regimen.
Does art reduce pain and stress? A registered report protocol of investigating autonomic and endocrine markers of music, visual art, and multimodal aesthetic experience
Authors: Fekete Anna , Maidhof Rosa M. , Specker Eva , Nater Urs M. , Leder Helmut
Published: April 2022

The pain- and stress-reducing effects of music are well-known, but the effects of visual art, and the combination of these two, are much less investigated. We aim to (1) investigate the pain- and (2) stress-reducing effects of multimodal (music + visual art) aesthetic experience as we expect this to have stronger effects than a single modal aesthetic experience (music/ visual art), and in an exploratory manner, (3) investigate the underlying mechanisms of aesthetic experience, and the (4) individual differences. In a repeated-measures design (music, visual art, multimodal aesthetic experience, control) participants bring self-selected “movingly beautiful” visual artworks and pieces of music to the lab, where pain and stress are induced by the cold pressor test. Activity of the pain and stress responsive systems are measured by subjective reports, autonomic (electrocardiography, electrodermal activity, salivary alpha-amylase) and endocrine markers (salivary cortisol).
Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults
Authors: Pronk A. C. , Seppala L. J. , Trajanoska K. , Stringa N. , van de Loo B. , de Groot L. C. P. G. M. , van Schoor N. M. , Koskeridis F. , Markozannes G. , Ntzani E. , Uitterlinden A. G. , Rivadeneira F. , Stricker B. H. , van der Velde N.
Published: April 2022

Background

Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users.

Methods

The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated.

Results

In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26–0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17–3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07–2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05–3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01–1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92–1.00).

Conclusion

This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.
The role of telepathology in diagnosis of pre-malignant and malignant cervical lesions: Implementation at a tertiary hospital in Northern Tanzania
Authors: Mremi Alex , Bentzer Nina Karnøe , Mchome Bariki , Mlay Joseph , Blaakær Jan , Rasch Vibeke , Schledermann Doris
Published: April 2022

Introduction

Adequate and timely access to pathology services is a key to scale up cancer control, however, there is an extremely shortage of pathologists in Tanzania. Telepathology (scanned images microscopy) has the potential to increase access to pathology services and it is increasingly being employed for primary diagnosis and consultation services. However, the experience with the use of telepathology in Tanzania is limited. We aimed to investigate the feasibility of using scanned images for primary diagnosis of pre-malignant and malignant cervical lesions by assessing its equivalency to conventional (glass slide) microscopy in Tanzania.

Methods

In this laboratory-based study, assessment of hematoxylin and eosin stained glass slides of 175 cervical biopsies were initially performed conventionally by three pathologists independently. The slides were scanned at x 40 and one to three months later, the scanned images were reviewed by the pathologists in blinded fashion. The agreement between initial and review diagnoses across participating pathologists was described and measured using Cohen’s kappa coefficient (κ).

Results

The overall concordance of diagnoses established on conventional microscopy compared to scanned images across three pathologists was 87.7%; κ = 0.54; CI (0.49–0.57).The overall agreement of diagnoses established by local pathologist on conventional microscopy compared to scanned images was 87.4%; κ = 0.73; CI (0.65–0.79). The concordance of diagnoses established by senior pathologist compared to local pathologist on conventional microscopy and scanned images was 96% and 97.7% respectively. The inter-observer agreement (κ) value were 0.93, CI (0.87–1.00) and 0.94, CI (0.88–1.00) for conventional microscopy and scanned images respectively.

Conclusions

All κ coefficients expressed good intra- and inter-observer agreement, suggesting that telepathology is sufficiently accurate for primary diagnosis in surgical pathology. The discrepancies in interpretation of pre-malignant lesions highlights the importance of p16 immunohistochemistry in definitive diagnosis in these lesions. Sustainability factors including hardware and internet connectivity are essential components to be considered before telepathology may be deemed suitable for widely use in Tanzania.
Relay cropping of cotton in wheat improves productivity of cotton-wheat cropping system
Authors: Tariq Muhammad , Afzal Muhammad Naveed , Ahmad Muhammad , Ahmed Zeeshan , Afzal Muhammad Umer , Maqbool Amir , Al-Hashimi Abdulrahman , Elshikh Mohamed S.
Published: April 2022

Cotton-wheat (CW) is an important cropping system in Pakistan; however, delayed cultivation of cotton after wheat significantly deceases system productivity. Late-sown cotton crop suffers from heat stress, high fruit shedding and infestation of various pests and cotton leaf curl virus (CLCV). Therefore, early sowing of cotton is preferred to overcome these challenges. However, cotton planting is overlapped with the harvesting of wheat crop in CW cropping system. Since fallow land is unavailable, relay intercropping of cotton in wheat crop seems a viable option for early planting. This three-year field study evaluated the role of relay cropping of cotton in improving the productivity of CW cropping system and lowering CLCV infestation. Wheat was planted in 22.5 cm rows with no row skipped (W1), one row skipped after every three (W2), and six rows (W3) for planting cotton in 0.75 and 1.50 m apart rows. Early cotton was planted in fallow land (C1) and standing wheat in 0.75 (C2) and 1.50 m (C3) apart rows and conventional planting after wheat harvesting (C4). Yield losses of wheat crop ranged from 8.16 to 19.81% in W3 and W2, respectively compared W1. However, C2 and C3 treatments improved cotton yield by 86.07% and 64.89% suppressed CLCV infestation by 68.14% and 65.86%, respectively compared to C4. Moreover, net benefits from relay cropping (W2C2) were 2190.1 $ ha-1 in 2013–14, 1954.4 $ ha-1 in 2014–15 and 2559.5 $ ha-1 in 2015–16 in comparison with C1 (1543.5, 1311.7 and 1892.3 $ ha-1 during 2013–14, 2014–15 and 2015–16, respectively). The W2 resulted in higher cotton yield compared to W3 which is mainly attributed to double number of cotton rows in W2 than W3. It is concluded that cotton relay cropping (W2C2) resulted in the highest economic returns with minimum CLCV infestation. Therefore, W2C2 is recommended for improving the system productivity of CW cropping system.
Two-way text message interventions and healthcare outcomes in Africa: Systematic review of randomized trials with meta-analyses on appointment attendance and medicine adherence
Authors: Ødegård Emilie S. , Langbråten Lena S. , Lundh Andreas , Linde Ditte S.
Published: April 2022

Background

The growing access to mobile phones in Africa has led to an increase in mobile health interventions, including an increasing number of two-way text message interventions. However, their effect on healthcare outcomes in an African context is uncertain. This systematic review aims to landscape randomized trials involving two-way text message interventions and estimate their effect on healthcare outcomes.

Methods

We searched Medline, Embase, Cochrane Central Register of Controlled Trials, The Global Health Library (up to 12 August 2021) and trial registries (up to 24 April 2020). Published and unpublished trials conducted in Africa comparing two-way text message interventions with standard care and/or one-way text message interventions were included. Trials that reported dichotomous effect estimates on healthcare appointment attendance and/or medicine adherence were assessed for risk of bias and included in meta-analyses. Results of other outcomes were reported descriptively.

Results

We included 31 trials (28,563 participants) all set in Sub-Saharan Africa with a wide range of clinical conditions. Overall, ten different trials were included in the primary meta-analyses, and two of these had data on both medicine adherence and appointment attendance. An additional two trials were included in sensitivity analyses. Of the 12 included trials, three were judged as overall low risk of bias and nine as overall high risk of bias trials. Two-way text messages did not improve appointment attendance, RR: 1.03; 95% CI: 0.95–1.12, I2= 53% (5 trials, 4374 participants) but improved medicine adherence compared to standard care, RR: 1.14, 95% CI: 1.07–1.21, I2= 8% (6 trials, 2783 participants).

Conclusion

Two-way text messages seemingly improve medicine adherence but has an uncertain effect on appointment attendance compared to standard care.

Systematic review registration

PROSPERO CRD42020175810.
Morphological characteristics and abundance of prokaryotes associated with gills in mangrove brachyuran crabs living along a tidal gradient
Authors: Garuglieri Elisa , Booth Jenny Marie , Fusi Marco , Yang Xinyuan , Marasco Ramona , Mbobo Tumeka , Clementi Emanuela , Sacchi Luciano , Daffonchio Daniele
Published: April 2022

Due to the chemico-physical differences between air and water, the transition from aquatic life to the land poses several challenges for animal evolution, necessitating morphological, physiological and behavioural adaptations. Microbial symbiosis is known to have played an important role in eukaryote evolution, favouring host adaptation under changing environmental conditions. We selected mangrove brachyuran crabs as a model group to investigate the prokaryotes associated with the gill of crabs dwelling at different tidal levels (subtidal, intertidal and supratidal). In these animals, the gill undergoes a high selective pressure, finely regulating multiple physiological functions during both animal submersion under and emersion from the periodical tidal events. We hypothesize that similarly to other marine animals, the gills of tidal crabs are consistently colonized by prokaryotes that may quantitatively change along the environmental gradient driven by the tides. Using electron microscopy techniques, we found a thick layer of prokaryotes over the gill surfaces of all of 12 crab species from the mangrove forests of Saudi Arabia, Kenya and South Africa. We consistently observed two distinct morphotypes (rod- and spherical-shaped), positioned horizontally and/or perpendicularly to the gill surface. The presence of replicating cells indicated that the prokaryote layer is actively growing on the gill surface. Quantitative analysis of scanning electron microscopy images and the quantification of the bacterial 16S rRNA gene by qPCR revealed a higher specific abundance of prokaryote cells per gill surface area in the subtidal species than those living in the supratidal zone. Our results revealed a correlation between prokaryote colonization of the gill surfaces and the host lifestyle. This finding indicates a possible role of prokaryote partnership within the crab gills, with potential effects on animal adaptation to different levels of the intertidal gradient present in the mangrove ecosystem.
Incidence, risk factors, and prognosis of acute kidney injury in hospitalized patients with acute cholangitis
Authors: Lee Tae Won , Bae Wooram , Kim Seongmin , Choi Jungyoon , Bae Eunjin , Jang Ha Nee , Chang Se-Ho , Park Dong Jun
Published: April 2022

Background

The association between acute cholangitis (AC) and acute kidney injury (AKI) remains unclear. We investigated the incidence, and clinical course of AKI in patients with AC, and the long-term prognosis.

Methods

We performed a single-center retrospective study of patients hospitalized with AC in a tertiary care center from January 2011 to December 2017. The risk factors for AKI were evaluated, and AKI severity was analyzed using the Systemic Inflammatory Response System (SIRS), quick sequential organ failure assessment (qSOFA) score, and 2018 Tokyo Guidelines (TG) grade. To calculate the relative risk of death based on AKI, hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained using Cox’s proportional hazard models.

Results

A total of 1,438 patients with AC were included, of whom 18.2% (n = 261) developed AKI. AKI patients were older, and had a lower systolic blood pressure and more comorbidities including hypertension (HT), chronic kidney disease, and cardiovascular accidents. Disease severity (as assessed by SIRS, qSOFA, and the Tokyo Guidelines grade) was higher in the AKI group, as was the in-hospital mortality rate. Multivariate analysis revealed that age, HT, SIRS and qSOFA scores ≥ 2, and TG grade of III were significant risk factors for AKI. Kaplan-Meier analysis revealed significantly higher mortality in the AKI than non-AKI group. AKI (HR = 1.853; 95% CI: 1.115–3.079) and TG grade III (HR = 2.139; 95% CI: 1.190–3,846) were independent predictors of all-cause AC mortality, even after adjusting for all covariates. The annual rate of decline in the estimated glomerular filtration rate was faster in the AKI than non-AKI group (2.9 ± 6.7 vs. 0.5 ± 5.3 mL/min/1.73 m2/year, p < 0.001).

Conclusions

AKI development increased AC severity and mortality. Our results suggest that clinicians should monitor AKI status and perform appropriate management as soon as possible.