bluuebunny/crossref_metadata_2025 huggingface dataset:
Loop-mediated isothermal amplification (LAMP) test in the detection of uncomplicated malaria in pregnancy: a meta-analysis of diagnostic accuracy
Authors: Yon Joseph Lee Teck , Htet Norah Htet , Naing Cho , Tung Wong Siew , Aung Htar Htar , Mak Joon Wah
Published: December 2022

Background

Due to relatively low malaria parasitaemia in pregnancy, an appropriate field test that can adequately detect infections in pregnant women presenting with illness or for malaria screening during antenatal care is crucially important. The objective was to evaluate the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for the detection of uncomplicated malaria in pregnancy.

Methods

This was a meta-analysis of diagnostic accuracy. Relevant studies that assessed the diagnostic performance of LAMP for the detection of malaria in pregnancy were searched in health-related electronic databases including PubMed, Ovid, and Google Scholar. The methodological quality of the studies included was evaluated using the QUADAS-2 tool.

Results

Of the 372 studies identified, eight studies involving 2999 pregnant women in five endemic countries that assessed the accuracy of LAMP were identified. With three types of PCR as reference tests, the pooled sensitivity of LAMP was 91% (95%CI 67–98%) and pooled specificity was 99% (95%CI 83–100%, 4 studies), and the negative likelihood ratio was 9% (2–40%). Caution is needed in the interpretation as there was substantial between-study heterogeneity (I2: 80%), and a low probability that a person without infection is tested negative. With microscopy as a reference, the pooled sensitivity of LAMP was 95% (95%CI 26–100%) and pooled specificity was 100% (95%CI 94–100%, 4 studies). There was a wide range of sensitivity and substantial between-study heterogeneity (I2: 83.5–98.4%). To investigate the source of heterogeneity, a meta-regression analysis was performed with covariates. Of these potential confounding factors, reference test (p: 0.03) and study design (p:0.03) had affected the diagnostic accuracy of LAMP in malaria in pregnancy. Overall, there was a low certainty of the evidence in accuracy estimates.

Conclusion

The findings suggest that LAMP is more sensitive than traditional tests used at facilities, but the utility of detecting and treating these low-density infections is not well understood. Due to the limited number of studies with bias in their methodological quality, variation in the study design, and different types of reference tests further research is likely to change the estimate. Well-conceived large prospective studies with blinding of the index test results are recommenced.
Nanomaterials meet surface-enhanced Raman scattering towards enhanced clinical diagnosis: a review
Authors: Yuan Kaisong , Jurado-Sánchez Beatriz , Escarpa Alberto
Published: December 2022

Surface-enhanced Raman scattering (SERS) is a very promising tool for the direct detection of biomarkers for the diagnosis of i.e., cancer and pathogens. Yet, current SERS strategies are hampered by non-specific interactions with co-existing substances in the biological matrices and the difficulties of obtaining molecular fingerprint information from the complex vibrational spectrum. Raman signal enhancement is necessary, along with convenient surface modification and machine-based learning to address the former issues. This review aims to describe recent advances and prospects in SERS-based approaches for cancer and pathogens diagnosis. First, direct SERS strategies for key biomarker sensing, including the use of substrates such as plasmonic, semiconductor structures, and 3D order nanostructures for signal enhancement will be discussed. Secondly, we will illustrate recent advances for indirect diagnosis using active nanomaterials, Raman reporters, and specific capture elements as SERS tags. Thirdly, critical challenges for translating the potential of the SERS sensing techniques into clinical applications via machine learning and portable instrumentation will be described. The unique nature and integrated sensing capabilities of SERS provide great promise for early cancer diagnosis or fast pathogens detection, reducing sanitary costs but most importantly allowing disease prevention and decreasing mortality rates.
Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats
Authors: Ceyzériat Kelly , Zilli Thomas , Millet Philippe , Koutsouvelis Nikolaos , Dipasquale Giovanna , Fossey Christine , Cailly Thomas , Fabis Frédéric , Frisoni Giovanni B. , Garibotto Valentina , Tournier Benjamin B.
Published: December 2022

Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01; soluble and aggregated forms of Aβ40, Aβ42, and Aβoligomers). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset.
Isolation, purification and PEG-mediated transient expression of mesophyll protoplasts in Camellia oleifera
Authors: Li Sufang , Zhao Rui , Ye Tianwen , Guan Rui , Xu Linjie , Ma Xiaoling , Zhang Jiaxi , Xiao Shixin , Yuan Deyi
Published: December 2022

Background

Camellia oleifera (C. oleifera) is a woody edible oil crop of great economic importance. Because of the lack of modern biotechnology research, C. oleifera faces huge challenges in both breeding and basic research. The protoplast and transient transformation system plays an important role in biological breeding, plant regeneration and somatic cell fusion. The objective of this present study was to develop a highly efficient protocol for isolating and purifying mesophyll protoplasts and transient transformation of C. oleifera. Several critical factors for mesophyll protoplast isolation from C. oleifera, including starting material (leaf age), pretreatment, enzymatic treatment (type of enzyme, concentration and digestion time), osmotic pressure and purification were optimized. Then the factors affecting the transient transformation rate of mesophyll protoplasts such as PEG molecular weights, PEG4000 concentration, plasmid concentration and incubation time were explored.

Results

The in vitro grown seedlings of C. oleifera ‘Huashuo’ were treated in the dark for 24 h, then the 1st to 2nd true leaves were picked and vacuumed at − 0.07 MPa for 20 min. The maximum yield (3.5 × 107/g·FW) and viability (90.9%) of protoplast were reached when the 1st to 2nd true leaves were digested in the enzymatic solution containing1.5% (w/v) Cellulase R-10, 0.5% (w/v) Macerozyme R-10 and 0.25% (w/v) Snailase and 0.4 M mannitol for 10 h. Moreover, the protoplast isolation method was also applicable to the other two cultivars, the protoplast yield for ‘TXP14’ and ‘DP47’ was 1.1 × 107/g·FW and 2.6 × 107/g·FW, the protoplast viability for ‘TXP14’ and ‘DP47’ was 90.0% and 88.2%. The purification effect was the best when using W buffer as a cleaning agent by centrifugal precipitation. The maximum transfection efficiency (70.6%) was obtained with the incubation of the protoplasts with 15 µg plasmid and 40% PEG4000 for 20 min.

Conclusion

In summary, a simple and efficient system for isolation and transient transformation of C. oleifera mesophyll protoplast is proposed, which is of great significance in various aspects of C. oleifera research, including the study of somatic cell fusion, genome editing, protein function, signal transduction, transcriptional regulation and multi-omics analyses.
Effects of cushion box and closed let-down ladder usage on damage to corn during handling: physiological deterioration
Authors: Shahbazi Reza , Shahbazi Feizollah
Published: December 2022

Background

Corn seeds have a high susceptibility to mechanical damage due to their large size and mass. The main purpose of this study was to evaluate the effects of the cushion box and closed let-down ladder usage in minimizing the negative influence of the free fall on the storage potential of corn seeds. Corn seeds were evaluated for the extent of physiological damage by measuring the seed deterioration by the accelerated aging test (percentage loss in germination in the accelerated aging test), using three drop methods (free fall, with cushion box, and with closed let-down ladder) at three drop heights (5, 10, and 15 m) and five different moisture contents (10, 15, 20 and 25%).

Results

The drop methods had a significant effect on the storage potential of corn seeds. Sample seeds dropped without a ladder (free fall) had a significantly higher average physiological quality loss of 13.87% (loss in accelerated aging germination). In the use of the cushion box, the average percentage loss in germination was calculated to be 11.38%, which was decreased by about 18% more than the free fall. Sample seeds dropped with the closed let-down ladder had a lower average percentage loss in the germination of 8.78%, which showed that the closed let-down ladder significantly helped to reduce mechanical damage to corn seeds by about 37% comparing free fall and by about 23% to the use of the cushion box. The amounts of loss in physiological quality of corn seeds increased significantly with increasing drop height and moisture content, but the use of the cushion box and closed let-down ladder systems somewhat reduced the adverse effect of the above factors. Empirical models were developed for the dependency of physiological damage to corn seeds due to the impact caused by free fall, on the drop height and moisture content at different drop methods.

Conclusions

To minimize mechanical damage to seeds as they fall into the bin, a let-down ladder should be installed in the bin so that it can receive seeds from the filling spout with minimum damage.
Identification of an emerging cucumber virus in Taiwan using Oxford nanopore sequencing technology
Authors: Dong Zi-Xuan , Lin Chian-Chi , Chen Yuh-Kun , Chou Chia-Cheng , Chen Tsung-Chi
Published: December 2022

Background

In June 2020, severe symptoms of leaf mosaic and fruit malformation were observed on greenhouse-grown cucumber plants in Xizhou Township of Changhua County, Taiwan. An unknown virus, designated CX-2, was isolated from a diseased cucumber sample by single lesion isolation on Chenopodium quinoa leaves. Identification of CX-2 was performed. Moreover, the incidence of cucumber viruses in Taiwan was also investigated.

Methods

Transmission electron microscopy was performed to examine virion morphology. The portable MinION sequencer released by Oxford Nanopore Technologies was used to detect viral sequences in dsRNA of CX-2-infected leaf tissue. The whole genome sequence of CX-2 was completed by Sanger sequencing and analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) with species-specific primers and indirect enzyme-linked immunosorbent assay (ELISA) with anti-coat protein antisera were developed for virus detection in the field [see Additional file 1].

Results

Icosahedral particles about 30 nm in diameter were observed in the crud leaf sap of CX-2-infected C. quinoa plant. The complete genome sequence of CX-2 was determined as 4577 nt long and shared 97.0–97.2% of nucleotide identity with that of two cucumber Bulgarian latent virus (CBLV) isolates in Iran and Bulgaria. Therefore, CX-2 was renamed CBLV-TW. In 2020–2022 field surveys, melon yellow spot virus (MYSV) had the highest detection rate of 74.7%, followed by cucurbit chlorotic yellows virus (CCYV) (32.0%), papaya ringspot virus virus watermelon type (PRSV-W) (10.7%), squash leaf curl Philippines virus (SLCuPV) (9.3%), CBLV (8.0%) and watermelon silver mottle virus (WSMoV) (4.0%). Co-infection of CBLV and MYSV could be detected in field cucumbers.

Conclusion

The emerging CBLV-TW was identified by nanopore sequencing. Whole genome sequence analysis revealed that CBLV-TW is closely related, but phylogenetically distinct, to two known CBLV isolates in Bulgaria and Iran. Detection methods including RT-PCR and indirect ELISA have been developed to detect CBLV and to investigate cucumber viruses in central Taiwan. The 2020–2022 field survey results showed that MYSV and CCYV were the main threats to cucumbers, with CBLV, SLCuPV and WSMoV were occasionally occurring.
Impact of the COVID-19 pandemic on alcohol or drug use symptoms and service need among youth: a cross-sectional sample from British Columbia, Canada
Authors: Marchand Kirsten , Liu Guiping , Mallia Emilie , Ow Nikki , Glowacki Krista , Hastings Katherine G. , Mathias Steve , Sutherland Jason M. , Barbic Skye
Published: December 2022

Background

Concerns about youth alcohol and drug use have risen since the declaration of the global COVID-19 pandemic due to the pandemic’s impact on known risk and protective factors for substance use. However, the pandemic’s immediate and long-term impact on youths’ substance use patterns has been less clear. Thus, this study sought to determine how the COVID-19 pandemic impacted alcohol or drug use and its risk and protective factors among youth accessing integrated youth services.

Methods

We conducted a repeated cross-sectional study of patient-reported outcomes data collected between May 2018 and February 2022 among youth (n = 6022) ages 10–24 accessing a provincial network of integrated youth services in Canada. The main exposure of interest was the COVID-19 pandemic (March 2020 – February 2022) compared with a pre-pandemic period (May 2018 – February 2020). As measured by the Global Appraisal of Individual Needs – Short Screener, outcomes included the average number of past month alcohol or drug use symptoms and past month likelihood of service need for alcohol/drug use (moderate/high vs. low need). Interrupted time series (ITS) examined change in average monthly alcohol/drug use symptoms between the pre- and pandemic periods. Stratified multivariable logistic regression investigated how the pandemic modified the effects of established risk/protective factors on likelihood of alcohol/drug use service need.

Results

Fifty-percent of youth met the criteria for moderate/high likelihood of alcohol/drug use service need, with the odds being 2.39 times (95% confidence interval = 2.04, 2.80) greater during the pandemic compared to the pre-pandemic period. Results from the ITS indicated significant immediate effects of the pandemic on monthly substance use symptoms (p = 0.01). Significant risk/protective factors for service need included exposure to violence, engagement in meaningful activities, and self-rated physical and mental health; and the direction of their effects remained consistent across pandemic and pre-pandemic periods.

Conclusions

This study demonstrated that the COVID-19 pandemic corresponded with increased alcohol or drug use among youth accessing integrated services. This signals an urgent need for increased clinical capacity in existing youth services and policies that can respond to risk/protective factors for substance use earlier.
Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome
Authors: Scott Anthony , Hernandez Felicia , Chamberlin Adam , Smith Cathy , Karam Rachid , Kitzman Jacob O.
Published: December 2022

Background

Lynch syndrome (LS) is a cancer predisposition syndrome affecting more than 1 in every 300 individuals worldwide. Clinical genetic testing for LS can be life-saving but is complicated by the heavy burden of variants of uncertain significance (VUS), especially missense changes.

Result

To address this challenge, we leverage a multiplexed analysis of variant effect (MAVE) map covering >94% of the 17,746 possible missense variants in the key LS gene MSH2. To establish this map’s utility in large-scale variant reclassification, we overlay it on clinical databases of >15,000 individuals with LS gene variants uncovered during clinical genetic testing. We validate these functional measurements in a cohort of individuals with paired tumor-normal test results and find that MAVE-based function scores agree with the clinical interpretation for every one of the MSH2 missense variants with an available classification. We use these scores to attempt reclassification for 682 unique missense VUS, among which 34 scored as deleterious by our function map, in line with previously published rates for other cancer predisposition genes. Combining functional data and other evidence, ten missense VUS are reclassified as pathogenic/likely pathogenic, and another 497 could be moved to benign/likely benign. Finally, we apply these functional scores to paired tumor-normal genetic tests and identify a subset of patients with biallelic somatic loss of function, reflecting a sporadic Lynch-like Syndrome with distinct implications for treatment and relatives’ risk.

Conclusion

This study demonstrates how high-throughput functional assays can empower scalable VUS resolution and prospectively generate strong evidence for variant classification.
Advances and opportunities in integrating economic and environmental performance of renewable products
Authors: Meramo Samir , Fantke Peter , Sukumara Sumesh
Published: December 2022

There is a growing global need to transition from a fossil-based to a bio-based economy to produce fuels, chemicals, food, and materials. In the specific context of industrial biotechnology, a successful transition toward a sustainable development requires not only steering investment toward a bioeconomy, but also responsibly introducing bio-based products with lower footprints and competitive market prices. A comprehensive sustainability assessment framework applied along various research stages to guide bio-based product development is urgently needed but currently missing. To support holistic approaches to strengthen the global bioeconomy, the present study discusses methodologies and provides perspectives on the successful integration of economic and environmental performance aspects to guide product innovation in biotechnology. Efforts on quantifying the economic and environmental performance of bio-based products are analyzed to highlight recent trends, challenges, and opportunities. We critically analyze methods to integrate Techno-Economic Assessment (TEA) and Life Cycle Assessment (LCA) as example tools that can be used to broaden the scope of assessing biotechnology systems performance. We highlight the lack of social assessment aspects in existing frameworks. Data need for jointly applying TEA and LCA of succinic acid as example commodity chemical are assessed at various Technology readiness levels (TRLs) to illustrate the relevance of the level of integration and show the benefits of the use of combined assessments. The analysis confirms that the implementation of integrated TEA and LCA at lower TRLs will provide more freedom to improve bio-based product’s sustainability performance. Consequently, optimizing the system across TRLs will guide sustainability-driven innovation in new biotechnologies transforming renewable feedstock into valuable bio-based products.
Evolutionary trade-offs associated with copy number variations in resistance alleles in Culex pipiens mosquitoes
Authors: Milesi Pascal , Claret Jean-Loup , Unal Sandra , Weill Mylène , Labbé Pierrick
Published: December 2022

Organophosphate and carbamate insecticides have largely been used worldwide to control mosquito populations. As a response, the same amino acid substitution in theace-1gene (G119S), conferring resistance to both insecticides, has been selected independently in many mosquito species. InAnopheles gambiae, it has recently been shown that the G119S mutation is actually part of homogeneous duplications that associate multiple resistance copies of theace-1gene. In this study, we showed that duplications of resistance copies of theace-1gene also exist in theCulex pipiensspecies complex. The number of copies is variable, and different numbers of copies are associated with different phenotypic trade-offs: we used a combination of bioassays and competition in population cages to show that having more resistance copies conferred higher resistance levels, but was also associated with higher selective disadvantage (or cost) in the absence of insecticide. These results further show the versatility of the genetic architecture of resistance to organophosphate and carbamate insecticides around theace-1locus and its role in fine-tuned adaptation to insecticide treatment variations.

Graphical Abstract
The presence of SARS-CoV-2 in multiple clinical specimens of a fatal case of COVID-19: a case report
Authors: Sokolovska Liba , Terentjeva-Decuka Anna , Cistjakovs Maksims , Nora-Krukle Zaiga , Gravelsina Sabine , Vilmane Anda , Vecvagare Katrine , Murovska Modra
Published: December 2022

Background

The risk of developing severe and even fatal coronavirus disease 2019 (COVID-19) increases with various factors such as advanced age and chronic diseases, especially those treated with immunosuppressive drugs. Viral ribonucleic acid (RNA) and viral load detection in extra-pulmonary specimens have been proposed to indicate disease severity.

Case presentation

Here we describe a fatal COVID-19 case of an 83-year-old Caucasian male patient with various underlying comorbidities, including cardiovascular and autoimmune disorders, as well as immunosuppression due to lymphoma treatment. Upon admission, the patient was radiologically diagnosed with severe COVID-19. The patient was febrile and presented with diarrhea, continued dyspnea, tachypnea, and low blood oxygen saturation, treated with high-concentration oxygen supplementation and antibacterial therapy. Overall the patient was treated for COVID-19 for 19 days. Blood tests were performed upon admission, on the fifth, 10th, 13th, and 19th day. In addition, nasopharyngeal swab, blood, urine, and fecal samples were collected from the patient on the 14th day for virological and immunological investigations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detectable in all samples collected from this patient, including blood plasma and peripheral blood mononuclear cells (PBMC), with very high viral loads. However, neither virus-specific IgA, IgM, nor IgG antibodies were detectable.

Conclusions

The various cardiovascular, autoimmune, and oncological disorders, advanced age, and the high levels of inflammatory markers predisposed the patient to severe COVID-19 and determined the fatal outcome of the disease. We believe that the multiple specimen SARS-CoV-2 positivity and extremely high viral loads in nasopharyngeal swab and fecal samples to be the result of COVID-19 severity, the inability of viral clearance and weakened immune response due to advanced age, comorbidities, and the presence of non-Hodgkin's lymphoma and the immunosuppressive treatment for it, highlighting the risks of COVID-19 in such patients.
Leaves litterfall and nutrient inputs from four multipurpose tree/shrub species of homegarden agroforestry systems
Authors: Kassa Gezahegn , Bekele Tamrat , Demissew Sebsebe , Abebe Tesfaye
Published: December 2022

Background

As compared to natural forest ecosystems, soils under agroecosystems are more subjected to changes in physical and biochemical attributes. But, tree species that are retained and/or planted on these agroecosystems replenish soil fertility through the influence of leaves litterfall quantity and quality. Tree species-related differences in the quantity and seasonality of leaves litterfall and the associated amounts of annual returns of nutrient elements were assessed from four multipurpose tree/shrub species (Erythrina bruceiSchweinf,Cordia africanaLam.,Grevillea robustaR. Br. andMalus sylvestrisMill.) in homegarden agroforestry systems. Five replicates of two leaf litterfall traps per species were randomly positioned beneath the subcanopy area for 12 months, totaling 40 litterfall traps distributed among the four species.

Results

The results of this study suggested that total annual leaves litterfall varied significantly among species (ranging from 171.18 to 962 kg ha− 1), with the combined per tree mean monthly (28.13 kg tree− 1), per tree annual (331.10 kg tree− 1 year− 1) and per area basis total annual (9439.33 kg ha− 1) leaves litterfall production. A clear seasonal leaves litterfall pattern with varying peaks was observed for the multipurpose tree/shrub species in the present study, with a bimodal distribution pattern forE. bruceiandC. africanaand a unimodal distribution pattern forG. robustaandM. sylvestris. Similarly, both the concentrations and inputs of nutrients from the leaves᾽ litterfall showed considerable variations among species (p < 0.05). Among the investigated species,C. africanaandE. bruceiwere found to be the best in terms of carbon (C) and nitrogen (N) return,G. robustathe best in terms of phosphorous (P) return, andC. africanaas well best for potassium (K) return. The combined mean annual nutrient inputs recorded for all the species were 3125.32 kg C ha− 1 year− 1, 149.70 kg N ha− 1 year− 1, 54.86 kg K ha− 1 year− 1, and 3.56 kg P ha− 1 year− 1.

Conclusions

Leaves litterfall amount differed among tree species as influenced by tree species characteristics (canopy area, diameter at breast height (DBH), height), but no cause-effect relationship with age and climate (monthly precipitation and temperature).
Lithium induced hypercalcemia: an expert opinion and management algorithm
Authors: Kovacs Zoltan , Vestergaard Peter , W. Licht Rasmus , P. V. Straszek Sune , Hansen Anne Sofie , H. Young Allan , Duffy Anne , Müller-Oerlinghausen Bruno , Seemueller Florian , Sani Gabriele , Rubakowski Janusz , Priller Josef , Vedel Kessing Lars , Tondo Leonardo , Alda Martin , Manchia Mirko , Grof Paul , Ritter Phillip , Hajek Tomas , Lewitzka Ute , Bergink Veerle , Bauer Michael , Nielsen René Ernst
Published: December 2022

Background

Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking.

Methods

Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment.

Results

In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed.

Conclusions

Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.
Numerical estimation of a tsunami source at the flexural area of Kuril and Japan Trenches in the fifteenth to seventeenth century based on paleotsunami deposit distributions in northern Japan
Authors: Sato Kai , Yamada Masaki , Ishimura Daisuke , Ishizawa Takashi , Baba Toshitaka
Published: December 2022

Paleotsunami deposit investigations and numerical tsunami computations have been performed to elucidate the source and size of large tsunamis along the Kuril to Japan Trenches, particularly for unusual tsunamis that occurred in the seventeenth century, the 1611 CE Keicho tsunami (M 8.1) along the Japan Trench and seventeenth-century tsunami (> Mw 8.8) along the Kuril Trench, which caused serious damages on the coastal residents and environments. Moreover, several paleotsunami deposits dating from the thirteenth to eighteenth centuries have been reported along the area between the Kuril and Japan subduction zones, but their sources have not been clarified. In this study, we estimated the tsunami sources from numerical simulations using the distribution of fifteenth- to seventeenth-century tsunami deposits at Sekinehama along the coast of the Shimokita Peninsula. Based on numerical simulations with previously proposed fault models, the tsunami deposits showing similar ages at Sekinehama and another site on the coast of Shimokita Peninsula, which are within 50 km apart, could not be explained except with the huge earthquake models (> Mw 9.1), whose rupture zones extend to not only the Kuril or Japan Trenches but also their flexural area. Thus, we modified or newly proposed twelve fault models located in the flexural area between the two trenches to explain tsunami deposits possibly around the seventeenth century at the above-mentioned two sites on the coast of Shimokita Peninsula. Simulations using these models elucidated that the rupture in the shallow or deep plate boundaries with > 14–32 m slip (> Mw 8.55–8.76) is necessary. If the tsunami deposits around the seventeenth century along the Iburi–Hidaka coast in Hokkaido and those at the two sites mentioned above might be left by an identical event, an interplate earthquake with > 18–40 m slip (> Mw 8.62–9.2) in the flexural area is needed. Moreover, this interplate earthquake might have occurred in the deep plate boundary than in the shallower plate boundary based on slip deficit and slow earthquake distribution data. Our results offer significant insights into a large earthquake (> M 8) along the Kuril and Japan Trenches in the fifteenth to seventeenth century.
Food safety practice and its associated factors among food handlers in food establishments of Mettu and Bedelle towns, Southwest Ethiopia, 2022
Authors: Tamiru Sanbato , Bidira Kebebe , Moges Tesema , Dugasa Milkias , Amsalu Bonsa , Gezimu Wubishet
Published: December 2022

Background

Food safety and hygiene are currently a global health concern, especially in unindustrialized countries, as a result of increasing food-borne diseases (FBDs) and accompanying deaths. It has continued to be a critical problem for people, food companies, and food control officials in developed and developing nations.

Objective

The objective of the study was to assess food safety practices and associated factors among food handlers in food establishments in Mettu and Bedelle towns, south-west Ethiopia, 2022.

Methods

A community-based cross-sectional study was conducted from February to March 2022, among 450 randomly selected food handlers working in food and drink establishments in Mettu and Bedelle towns, Southwest Ethiopia. Data was collected using an interviewer-administered structured questionnaire. The data was coded and entered into Epi Data version 3.1 before being exported to SPSS version 20 for analysis. Both bivariate and multivariable logistic regression models were fitted. An adjusted odds ratio and a 95% confidence level were estimated to assess the significance of associations. A p-value of < 0.05 was considered sufficient to declare the statistical significance of variables in the final model.

Result

A total of 450 food handlers participated in the study, making the response rate 99.3%. About 202 (44.9%) of respondents had poor practices in food safety. Lack of supervision (AOR = 6.2, 95% CI: 3.37, 11.39), absence of regular medical checkups (AOR = 1.98; 95% CI: 1.14, 3.43), lack of knowledge of food safety practices (AOR =2.32; 95% CI: 1.38, 3.89), availability of water storage equipment (AOR =0.37; CI: 0.21, 0.64), and unavailability of a refrigerator (AOR =0.24; 95% CI: 0.12) were factors significantly associated with food safety practices.

Conclusion

The level of poor food safety practices was remarkably high. Knowledge of food safety, medical checkups, service year as food handler, availability of water storage equipment, availability of refrigerator, and sanitary supervision were all significantly associated with food safety practice. Hence, great efforts are needed to improve food safety practices, and awareness should be created for food handlers on food safety.
Targeted validation: validating clinical prediction models in their intended population and setting
Authors: Sperrin Matthew , Riley Richard D. , Collins Gary S. , Martin Glen P.
Published: December 2022

Clinical prediction models must be appropriately validated before they can be used. While validation studies are sometimes carefully designed to match an intended population/setting of the model, it is common for validation studies to take place with arbitrary datasets, chosen for convenience rather than relevance. We call estimating how well a model performs within the intended population/setting “targeted validation”. Use of this term sharpens the focus on the intended use of a model, which may increase the applicability of developed models, avoid misleading conclusions, and reduce research waste. It also exposes that external validation may not be required when the intended population for the model matches the population used to develop the model; here, a robust internal validation may be sufficient, especially if the development dataset was large.
The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development
Authors: Yan Weizhu , Zheng Yanhui , Dou Chao , Zhang Guixiang , Arnaout Toufic , Cheng Wei
Published: December 2022

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a tenacious pathogen that has latently infected one third of the world’s population. However, conventional TB treatment regimens are no longer sufficient to tackle the growing threat of drug resistance, stimulating the development of innovative anti-tuberculosis agents, with special emphasis on new protein targets. The Mtb genome encodes ~4000 predicted proteins, among which many enzymes participate in various cellular metabolisms. For example, more than 200 proteins are involved in fatty acid biosynthesis, which assists in the construction of the cell envelope, and is closely related to the pathogenesis and resistance of mycobacteria. Here we review several essential enzymes responsible for fatty acid and nucleotide biosynthesis, cellular metabolism of lipids or amino acids, energy utilization, and metal uptake. These include InhA, MmpL3, MmaA4, PcaA, CmaA1, CmaA2, isocitrate lyases (ICLs), pantothenate synthase (PS), Lysine-ε amino transferase (LAT), LeuD, IdeR, KatG, Rv1098c, and PyrG. In addition, we summarize the role of the transcriptional regulator PhoP which may regulate the expression of more than 110 genes, and the essential biosynthesis enzyme glutamine synthetase (GlnA1). All these enzymes are either validated drug targets or promising target candidates, with drugs targeting ICLs and LAT expected to solve the problem of persistent TB infection. To better understand how anti-tuberculosis drugs act on these proteins, their structures and the structure-based drug/inhibitor designs are discussed. Overall, this investigation should provide guidance and support for current and future pharmaceutical development efforts against mycobacterial pathogenesis.
Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study
Authors: Bassatne Aya , Murad Mohammad H , Piggott Thomas , Drake Matthew T , Rahme Maya , El-Hajj Fuleihan Ghada
Published: December 2022

Background

Integrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM).

Objective

Evaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults.

Methods

We followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility.

Results

In the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes.

Conclusion

Using mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.
A Systematic Review Supporting the Endocrine Society Clinical Practice Guideline on the Treatment of Hypercalcemia of Malignancy in Adults
Authors: Seisa Mohamed O , Nayfeh Tarek , Hasan Bashar , Firwana Mohammed , Saadi Samer , Mushannen Ahmed , Shah Sahrish H , Rajjoub Noora S , Farah Magdoleen H , Prokop Larry J , Wang Zhen , Fuleihan Ghada El-Hajj , Drake Matthew T , Murad Mohammad Hassan
Published: December 2022

Context

Hypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.

Objective

To support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.

Methods

We searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.

Results

We reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.

Conclusion

The evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients’ values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.
β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT
Authors: Galderisi Alfonso , Evans-Molina Carmella , Martino Mariangela , Caprio Sonia , Cobelli Claudio , Moran Antoinette
Published: December 2022

Context

The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT).

Objective

Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI.

Methods

We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies.

Results

The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P < .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P < .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (−35.3 to 32.5), 0.2% (−0.6 to 1.3), and 14.9% (−1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components.

Conclusion

The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.
Low T3 Syndrome on Admission and Response to Nutritional Support in Malnourished Medical Inpatients
Authors: Müller Natasha Anouschka , Kaegi-Braun Nina , Durmisi Mirsada , Gressies Carla , Tribolet Pascal , Stanga Zeno , Mueller Beat , Schuetz Philipp
Published: December 2022

Context

During illness, deiodination of thyroxine (T4) to triiodothyronine (T3) is downregulated. This is called “low T3 syndrome”, an adaptive metabolic mechanism to reduce energy expenditure and prevent catabolism.

Objective

We aimed to investigate the prognostic role of low T3 syndrome in patients at nutritional risk regarding mortality, clinical outcomes, and response to nutritional support.

Methods

This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled, Swiss, multicenter trial comparing effects of individualized nutritional support with usual care in adult medical inpatients at nutritional risk. The primary endpoint was all-cause mortality over 30, 180 days, and 5 years.

Results

We had complete data including fT3 concentration of 801/2028 (39.5%) patients from the initial trial. Of these 492 (61.4%) had low T3 syndrome (fT3 < 3.2 pmol/L). Low T3 syndrome was associated with higher mortality over 30 days (adjusted hazard ratio 1.97, 95% CI 1.17-3.31, P = .011) and other adverse clinical outcomes. Nutritional support only lowered mortality in the group of patients with low T3 syndrome but not in those without low T3 syndrome (adjusted odds ratio of nutritional support of 0.82 [95% CI 0.47-1.41] vs 1.47 [95% CI 0.55-3.94]). This finding, however, was not significant in interaction analysis (P for interaction = .401).

Conclusion

Our secondary analysis of a randomized trial suggests that medical inpatients at nutritional risk with low T3 syndrome have a substantial increase in mortality and may show a more pronounced beneficial response to nutritional support interventions.
Accumulation in Visceral Adipose Tissue Over 6 Years Is Associated With Lower Paraspinal Muscle Density
Authors: Liu Ching-Ti , Tsai Timothy , Allaire Brett T , Bouxsein Mary L , Hannan Marian T , Travison Thomas G , Kiel Douglas P
Published: December 2022

Context

Visceral adipose tissue (VAT) has been recognized to be a metabolically active fat depot that may have paracrine effects on surrounding tissues, including muscle. Since many adults accumulate VAT as they age, the effect of changes in VAT on muscle is of interest.

Objective

We determined the association between 6-year changes in VAT and paraspinal muscle density, an indicator of fatty infiltration.

Methods

This study included 1145 participants from the Framingham Study third-generation cohort who had both quantitative computed tomography scans of the spine at baseline and 6-year's follow-up, on whom muscle density was measured along with VAT. We implemented multiple regression to determine the association of muscle density at follow-up as primary outcome measure with changes in VAT (follow-up minus baseline divided by 100), adjusting for VAT at baseline, age, sex, height, menopausal status, presence of diabetes, and physical activity. Analyses were performed in men and women separately.

Results

After adjustment for covariates, individuals with the greatest accumulation of VAT over 6 years had significantly lower paraspinal density at the follow-up with an estimated 0.302 (95% CI, −0.380 to −0.224) and 0.476 (95% CI: −0.598 to −0.354) lower muscle density (HU) per 100-cm3 increase in VAT (both P values < .001) in men and women, respectively.

Conclusion

These results highlight that age-related accumulation of VAT in men and women is associated with lower muscle density. VAT may represent a modifiable risk factor for poor musculoskeletal outcomes with aging.