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Microbial fermentation has emerged as a pivotal process for sustainable production of essential goods and chemicals. Corynebacterium glutamicum is a proficient platform organism that contributes significantly to amino acid production through microbial fermentation. Despite its recognized safety, challenges persist in efficiently biosynthesizing natural products compared with other organisms. This study evaluated the safety of biomass products from bioengineered C. glutamicum through two different toxicological studies: a bacterial reverse mutation test (AMES test) and an acute oral toxicity test in rats. Three types of dried fermentation biomass products, each engineered for the enhanced production of specific amino acids (L-lysine, L-threonine, and L-tryptophan), were examined. The tests were conducted in compliance with Organization for Economic Co-operation and Development guidelines and revealed no mutagenicity or acute toxicity at the tested doses. These findings suggest the safety of biomass products from bioengineered C. glutamicum as potential feed materials, although further toxicity studies are recommended for comprehensive evaluation. This study underscores the importance of stringent safety assessments for advancing biotechnological applications and provides valuable insights into the potential utilization of microbial fermentation products in various industries. Moreover, this study highlights the significance of regulatory compliance and adherence to international standards to ensure the safety and efficacy of novel biotechnological products.

Although plant disease recognition has witnessed a significant improvement with deep learning in recent years, a common observation is that current deep learning methods with decent performance tend to suffer in real-world applications. We argue that this illusion essentially comes from the fact that current plant disease recognition datasets cater to deep learning methods and are far from real scenarios. Mitigating this illusion fundamentally requires an interdisciplinary perspective from both plant disease and deep learning, and a core question arises. What are the characteristics of a desired dataset? This paper aims to provide a perspective on this question. First, we present a taxonomy to describe potential plant disease datasets, which provides a bridge between the two research fields. We then give several directions for making future datasets, such as creating challenge-oriented datasets. We believe that our paper will contribute to creating datasets that can help achieve the ultimate objective of deploying deep learning in real-world plant disease recognition applications. To facilitate the community, our project is publicly available at https://github.com/xml94/PPDRD with the information of relevant public datasets.

Abstract Background Toll-like receptor 4 (TLR4) conducts a highly regulated inflammatory process by limiting the extent of inflammation to avoid toxicity and tissue damage, even in bone tissues. Thus, it is plausible that strategies for the maintenance of normal bone-immunity to prevent undesirable bone damage by TLR4 activation can exist, but direct evidence is still lacking. Methods Osteoclast precursors (OCPs) obtained from WT or Slit3-deficient mice were differentiated into osteoclast (OC) with macrophage colony-stimulating factor (M-CSF), RANK ligand (RANKL) and lipopolysaccharide (LPS) by determining the number of TRAP-positive multinuclear cells (TRAP+ MNCs). To determine the alteration of OCPs population, fluorescence-activated cell sorting (FACS) was conducted in bone marrow cells in mice after LPS injection. The severity of bone loss in LPS injected WT or Slit3-deficient mice was evaluated by micro-CT analysis. Result We demonstrate that TLR4 activation by LPS inhibits OC commitment by inducing the concomitant expression of miR-218–2-3p and its host gene, Slit3, in mouse OCPs. TLR4 activation by LPS induced SLIT3 and its receptor ROBO1 in BMMs, and this SLIT3-ROBO1 axis hinders RANKL-induced OC differentiation by switching the protein levels of C/EBP-β isoforms. A deficiency of SLIT3 resulted in increased RANKL-induced OC differentiation, and the elevated expression of OC marker genes including Pu.1, Nfatc1, and Ctsk. Notably, Slit3-deficient mice showed expanded OCP populations in the bone marrow. We also found that miR-218–2 was concomitantly induced with SLIT3 expression after LPS treatment, and that this miRNA directly suppressed Tnfrsf11a (RANK) expression at both gene and protein levels, linking it to a decrease in OC differentiation. An endogenous miR-218–2 block rescued the expression of RANK and subsequent OC formation in LPS-stimulated OCPs. Aligned with these results, SLIT3-deficient mice displayed increased OC formation and reduced bone density after LPS challenge. Conclusion Our findings suggest that the TLR4-dependent concomitant induction of Slit3 and miR-218–2 targets RANK in OCPs to restrain OC commitment, thereby avoiding an uncoordinated loss of bone through inflammatory processes. These observations provide a mechanistic explanation for the role of TLR4 in controlling the commitment phase of OC differentiation. Video Abstract

Objective To explore the nuanced relationship between sleep patterns, chronotype, quality and the influence of health and lifestyle factors on cognitive performance.Design, setting, participants This cross-sectional analysis used ordinary least squares regression within the UK Biobank database, assessing 26 820 participants aged 53–86 years, categorised into two cohorts: Cohort 1 (10 067 participants, 56% female; completed all four cognitive tests of Fluid Intelligence/reasoning, Pairs Matching, Reaction Time and Prospective Memory) and Cohort 2 (16 753 participants, 56% female; completed only two cognitive assessments of Pairs Matching and Reaction Time).Exposures Participant’s self-reported sleep duration, chronotype and quality. Cognitive function was assessed through standardised computerised tests. The analysis was adjusted for demographic and comorbidity covariates.Main outcomes and measures Cognitive performance scores were evaluated against sleep parameters and health and lifestyle factors including sex, age, vascular and cardiac conditions, diabetes, alcohol intake, smoking habits and body mass index.Results The regression highlighted a positive association between normal sleep duration (7–9 hours) and cognitive scores in Cohort 1 (β=0.0567, 95% CI 0.0284 to 0.0851), while extended sleep duration negatively impacted scores across both cohorts (Cohort 1: β=−0.188, 95% CI −0.2938 to −0.0822; Cohort 2: β=−0.2619, 95% CI −0.3755 to −0.1482). Chronotype distinctions, particularly intermediate and evening types, were linked to superior cognitive function. Gender, age, angina, high blood pressure, diabetes, alcohol intake and smoking emerged as significant cognitive influencers.Conclusions and relevance The study delineates a multifaceted and nuanced relationship between sleep variables, health and lifestyle factors in determining cognitive outcomes. These findings highlight the vital role of sleep quality on cognitive health.

Objectives This study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last 10 years.Methods This is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses and prescribed amounts for sleep disorders were recorded.Results The prevalence of sleep disorders increased from 3 867 975 (7.62%) in 2011 to 7 446 846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9 011 692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine.Conclusions Sleep disorders are continuously increasing, as is the use of medical services—personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognised as a significant health problem that needs to be actively addressed to improve quality of life.

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes.

This study aims to introduce a sea ice elevation dataset estimated by using a 3-D laser scanner during the ice camp of the 2022 Arctic summer field survey. The equipment used is FARO’s Laser scanner FOCUS 3D X 130 HDR. The observed sea ice floe is located in the Arctic Ocean (76°13' N, 174°35') and is a multi-year ice with several melt ponds and ice ridges. We scanned eight sections separately, considering the equipment’s maximum horizontal scan range and the ice surface’s topographic features. The raw data were co-registered based on the positions of reference spheres. The result indicated a significant level of accuracy with a target-based vertical mean error of 4.8 mm. The laser scanner data were merged into point clouds ranging from 160×210 m. As a result, sea ice elevation data were generated in 0 to 2.8 m based on the minimum vertical point in the observation range. Sea ice elevation data is an essential variable in estimating the various properties of sea ice, such as ice thickness and roughness. In addition, using climatic variables such as air temperature and energy budget observed simultaneously can help to understand the physical interaction between the sea ice surface and the atmosphere on a local scale.

Sea ice is monitored on a regular basis by satellite observation; however, image-based drift tracking is imprecise as the time interval forming the image-pair is too large to capture the actual trajectory of ice drift. In this study, drift trajectory and speed of an Arctic sea ice floe measured by a GPS tracker for 3 months and the characteristics of the relating device and data, are introduced.

Objectives: The CoV2-001 phase I randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up. Design: A total of 45 vaccine-naïve participants were recruited between December 31, 2020, and March 30, 2021. GLS-5310, encoding for the SARS-CoV-2 spike and open reading frame 3a (ORF3a) proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations. Results: GLS-5310 was well tolerated with no serious adverse events reported. Antibody and T cell responses were dose-independent. Anti-spike antibodies were induced in 95.5% of participants with an average geometric mean titer of ∼480 four weeks after vaccination and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination geometric mean titer of 28.4. T cell responses were induced in 97.8% of participants, averaging 716 site forming units/106 cells four weeks after vaccination, increasing to 1248 at week 24, and remaining greater than 1000 through 48 weeks. Conclusion: GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

Abstract Background Many countries are trying to integrate traditional and complementary medicine (T&CM) into their health care systems. However, it is not easy to integrate T&CM within a given health care system. This study aims to draw policy outcomes and lessons from the case of Malaysia, which has been making efforts for over 20 years to integrate various types of T&CM into the national health care system (NHS). Methods Documents were searched in major databases and websites using words such as Malaysia and T&CM, and additional documents were secured using snowballing techniques. Data were classified and organized according to the World Health Organization health systems framework. Results Malaysia has focused on managing the safety and quality of T&CM, and to that end it has been institutionalized by enacting specialized laws rather than by applying existing medical law directly. Malaysia was able to institutionalize T&CM by adopting a step-by-step approach that considered the appropriateness of administrative policies and measures. Conclusions Malaysia's experiences in implementing its T&CM policies will raise practical implications for countries struggling to integrate their existing T&CM into the NHS and utilize it for universal health coverage.

The subchronic toxicity of oral L-tryptophan produced by fermentation with metabolically engineered Corynebacterium glutamicum was evaluated in Sprague-Dawley rats. Doses of 0, 500, 1000, and 2000 mg/kg/day were administered to groups of 10 male and 10 female rats for 90 days. For the groups administered 0 and 2000 mg/kg/day, an additional 5 male and 5 female rats were tested as a recovery group. No adverse effects associated with the test substance were observed in all rats during the 90-day administration of the product, irrespective of dose, and at 4 weeks of recovery at dosages of 0 and 2000 mg/kg/day. Furthermore, histochemical and immunohistochemical analyses for L-tryptophan-associated eosinophilia-myalgia syndrome (EMS) did not reveal significant changes in both sexes of groups administered 0 or 2000 mg/kg/day. Based on these results, it could be concluded that there were no significant adverse effects related to the test substance in all animals; therefore, dried L-tryptophan fermentation product can be used as feed additive material.

The Nordic Seas have been widely implicated by deep water formation as a part of Atlantic Meridional Overturning Circulation. This study explores the spatiotemporal variations in the near-surface salinity over the Nordic Seas associated with surface freshening factors by using monthly TOPAZ4 reanalysis data from 1991 to 2019. We first show that reliability of TOPAZ4 data compared to the salinity products of other reanalysis data, satellite data, and in-situ measurements in the Nordic Seas. The salinity variability was larger in the Greenland Sea (GS) than in the Norwegian Sea (NS) on both time scales of seasonal and interannual. The seasonal change of GS salinity was coincident with the seasonality of sea ice extent. The longer-time variations are decomposed by empirical orthogonal function (EOF) analysis. The GS salinity is mainly affected by current advection (29%) and sea ice extent (11%). The interannual response of salinity to the sea ice extent over the GS differs by season. NS salinity variability responds to the strength of the Subpolar Gyre associated with a large-scale atmospheric system that caused the freshening event in the mid-1990s. The propagation of the northward Atlantic Water core is observed over the period of about 3 years from the Faroe Shetland Channel to the Fram Strait at a speed of 2.6-6.5° year-1. Other freshening factors such as sea ice export from the Arctic, freshwater flux at the Fram Strait, and net precipitation are also discussed. For the past three decades, the continuous trend appeared only in the sea ice extent, which might be a signal of climate changes over high latitude. However, there was no significant trend other than the periodic change in a few years to the decadal time scale in the salinity of GS and NS. As preconditioning for deep convection, near-surface salinity within Greenland Sea Gyre was influenced by salinity fluctuation in both GS and NS.

Mesenchymal stem cells (MSCs) show a decline in pluripotency and differentiation with increased cell culture passages in 2D cultures. The 2D monolayer culture fails to correctly imitate the architecture and microenvironments of in-vivo cell models. Alternatively, 3D culture may improve the simulations of in-vivo cell microenvironments with wide applications in cell culture and drug discovery. In the present study, we compared various 3D culturing techniques such as 3D micro-well (3D-S), hanging drop (HD), and ultra-low attachment (ULA) plate-based spheroid culture to study their effect on morphology, viability, pluripotency, cell surface markers, immunomodulatory factors, and differentiation capabilities of Wharton’s jelly-mesenchymal stem cells (WJ-MSCs). The cell morphology, viability, and senescence of 3D cultured WJ-MSCs were comparable to cells in 2D culture. The expression of pluripotency markers (OCT4, SOX2, and NANOG) was enhanced upto 2–8 fold in 3D cultured WJ-MSCs when compared to 2D culture. Moreover, the immunomodulatory factors (IDO, IL-10, LIF, ANG1, and VEGF) were significantly elevated in ULA based 3D cultured WJ-MSCs. Furthermore, significant enhancement in the differentiation potential of WJ-MSCs towards adipocyte (ADP and C/EBP-α), osteocyte (OPN and RUNX2), and definitive endodermal (SOX17, FOXA2, and CXCR4) lineages in 3D culture conditions were observed. Additionally, the osteogenic and adipogenic differentiation potential of WJ-MSCs over the time points 7 days, 14 days, and 28 days was also significantly increased in 3D culture groups. Our study demonstrates that stemness properties of WJ-MSCs were significantly enhanced in 3D cultures and ULA-based culture outperformed other methods with high pluripotency gene expression and enhanced differentiation potential. This study indicates the efficacy of 3D cultures to bridge the gap between 2D cell culture and animal models in regenerative medicine.

Objective To identify factors associated with accessing and utilisation of healthcare and provision of health services in slums.Design A scoping review incorporating a conceptual framework for configuring reported factors.Data sources MEDLINE, Embase, CINAHL, Web of Science and the Cochrane Library were searched from their inception to December 2021 using slum-related terms.Eligibility criteria Empirical studies of all designs reporting relevant factors in slums in low and middle-income countries.Data extraction and synthesis Studies were categorised and data were charted according to a preliminary conceptual framework refined by emerging findings. Results were tabulated and narratively summarised.Results Of the 15 469 records retrieved from all years, 4368 records dated between 2016 and 2021 were screened by two independent reviewers and 111 studies were included. The majority (63 studies, 57%) were conducted in Asia, predominantly in India. In total, 104 studies examined healthcare access and utilisation from slum residents’ perspective while only 10 studies explored provision of health services from providers/planners’ perspective (three studies included both). A multitude of factors are associated with accessing, using and providing healthcare in slums, including recent migration to slums; knowledge, perception and past experience of illness, healthcare needs and health services; financial constraint and competing priorities between health and making a living; lacking social support; unfavourable physical environment and locality; sociocultural expectations and stigma; lack of official recognition; and existing problems in the health system.Conclusion The scoping review identified a significant body of recent literature reporting factors associated with accessing, utilisation and provision of healthcare services in slums. We classified the diverse factors under seven broad categories. The findings can inform a holistic approach to improving health services in slums by tackling barriers at different levels, taking into account local context and geospatial features of individual slums.Systematic review registration number https://osf.io/694t2.

Abstract For mitigation strategies of an influenza outbreak, it can be helpful to understand the characteristics of regional and age-group-specific spread. In South Korea, however, there has been no official statistic related to it. In this study, we extract the time series of influenza incidence from National Health Insurance Service claims database, which consists of all medical and prescription drug-claim records for all South Korean population. The extracted time series contains the number of new patients by region (250 city-county-districts) and age-group (0–4, 5–19, 20–64, 65+) within a week. The number of cases of influenza (2009–2017) is 12,282,356. For computing an onset of influenza outbreak by region and age-group, we propose a novel method for early outbreak detection, in which the onset of outbreak is detected as a sudden change in the time derivative of incidence. The advantage of it over the cumulative sum and the exponentially weighted moving average control charts, which have been widely used for the early outbreak detection of infectious diseases, is that information on the previous non-epidemic periods are not necessary. Then, we show that the metro area and 5–19 age-group are earlier than the rural area and other age-groups for the start of the influenza outbreak. Also, the metro area and 5–19 age-group peak earlier than the rural area and other age-groups. These results would be helpful to design a surveillance system for timely early warning of an influenza outbreak in South Korea.

This study proposes a new assistive device for the blind that uses more than one-dimensional data to draw objects. The study aims to convert three-dimensional (3-D) spatial information into sound information using 6-axis and ultrasonic sensors, and to draw a 3-D depiction of the space ahead for the user. Fourteen participants were involved in testing, wherein 4 were visually impaired. Moreover, the male to female ratio was 7:3, with the average age of participants at 28.8 years. An initial sound recognition experiment was designed to assess the device's accuracy through participant use. Recognition rates were 70% for normal participants and 88% for the blind participants. Additional experiments expanded the environmental conditions by requiring participants to discern the distances of 10 objects, positioned at both high and low locations. Two different scenarios were employed: stationary and walking scenarios. The stationary distance measurement participants scored an average of 96 points, while the walking participants averaged 81 points. Under the given conditions, this study found that its assistive device for the visually impaired can draw a 3-D space with 88.5% accuracy. This probability promises a basic level of utility that can assist those with visual impairment in controlled environments, such as hospitals and homes.

In this study, to determine the spatiotemporal variability of satellite-observed chlorophyll-a (Chl-a) concentrations in the East Sea (Japan Sea, EJS), monthly composite images were generated via noise processing using Level-2 MODIS Chl-a data from 2003 to 2020. Harmonic analysis was performed on time-series Chl-a data to present the spatial distribution of seasonal and intraseasonal variability with 1–4 cycles per year. In the EJS, seasonal cycles contributed less than approximately 30% to the total variance in Chl-a variability, indicating the existence of dominant interannual variability. Analysis of the temporal trend in Chl-a concentrations showed that they increased (< 0.06 mg m–3 yr–1) in most of the EJS over almost two decades (2003–2020). In recent years, in the areas showing positive trends in Chl-a, it tended to increase with time, especially in the northern part of the EJS. As a result of examining the trend associated with the physical environment that affects the long-term trend in Chl-a concentrations, sea surface temperature (SST) trends were mostly increased. The wind speeds showed a characteristic strengthening trend in the northeastern part of the EJS and the North Korean coast. Long-term changes in wind direction indicated strengthening of the northerly wind components on the Russian coast and the westerly components on the eastern coast of the Korean Peninsula. These wind changes were closely related to the Arctic Oscillation (AO) index variability in relation to the recent warming of the Arctic Ocean. When the AO index was greater than 1, the wind speed tended to be weakened and the SSTs showed a tendency to increase. This led to general increasing responses in Chl-a concentrations during positive AO. The summer SST anomaly revealed an inverse relationship between higher positive values during the La Niña period and lower ones during the El Niño period. When the amplitude of MEI (Multi-variate ENSO Index) was high (| MEI| > 1), the SST anomaly indicated an inverse correlation with the Chl-a concentration anomaly in the EJS. This study demonstrated the regional effects of climate change on Chl-a variability in the EJS in response to tropical–subtropical and arctic–subarctic interactions between ocean and atmospheric variations.

This study evaluated the effect of various growth factors and hormones in an in vitro growth (IVG) medium on the in vitro maturation (IVM) and developmental competence of oocytes derived from small antral follicles (SAFs) in pigs. Cumulus–oocyte complexes (COCs) derived from SAFs were either untreated or treated with epidermal growth factor (EGF), insulin-like factor-1 (IGF-1), insulin, or growth hormone (GH) for 2 days of IVG. Following IVG, COCs were cultured for maturation, and IVM oocytes were induced for parthenogenesis (PA). During IVG, the nuclear maturation of oocytes was significantly increased by the insulin treatment compared to other treatments. Moreover, the insulin treatment significantly increased blastocyst formation after PA relative to the No-IVG, control, EGF, and GH treatments. The cumulus expansion score after IVG-IVM was significantly higher in the insulin group than in the other groups. The glutathione (GSH) contents in IVM oocytes were increased through treatment with IGF, insulin, and GH compared to those of No-IVG oocytes. The level of reactive oxygen species (ROS) in IVM oocytes in all treatment groups was significantly lower after IVG culture than in the No-IVG group. The maturation-promoting factor (MPF) activity after IVM in the insulin-treated oocytes was significantly higher than that of the oocytes treated with EGF, IGF-1, and GH. In conclusion, this study demonstrates that insulin treatment during IVG culture improves the maturational and developmental competence of oocytes derived from SAFs in pigs through its effect on cumulus cell expansion and cytoplasmic microenvironments, such as GSH, ROS, and MPF activity.

(1) Background: Contrary to a tenet of the funnel-shaped pediatric larynx with the cricoid level being narrowest, recent studies show the glottis and subglottis as the narrowest levels. To locate the functionally narrowest level of the larynx, we reported normal laryngeal dimensions and their croup-related changes in young children. (2) Methods: We reviewed normal plain neck radiographs recorded for the evaluation of minor trauma or foreign bodies in 504 children aged ≤4 years who visited the emergency department from 2016 through 2021. Using computed tomography-based localization of the glottis, we radiographically defined the subglottis and cricoid. At these levels, we measured diameters and calculated cross-sectional areas (CSAs) on the radiographs. The values were compared to the equivalent values of a 1:1 age-matched population with croup. (3) Results: In the study population (n = 401), the narrowest diameter and CSA were observed in the glottis. In detail, the mean anteroposterior/transverse diameters were 9.8/3.4 mm at the glottis, 8.5/5.6 mm at the subglottis, and 7.4/6.8 mm at the cricoid (p < 0.001), respectively. In the same order, the mean CSAs were 26.5, 38.1, and 40.5 mm2 (p < 0.001). All dimensions were narrower in the croup population (p < 0.001). We found croup-related narrowing, namely reductions in the transverse diameter and CSA that were more severe closer to the glottis (p < 0.001), without differences per level in the anteroposterior diameter. (4) Conclusions: This study confirms the glottis as the narrowest level of the larynx in young children. In addition, level-based differences in croup-related narrowing suggest some point between the glottis and subglottis as the functionally narrowest level.

Background: Prehypertension and hypertension are associated with cardiovascular disease, ischemic heart disease, and stroke morbidity. The purpose of this study is to evaluate the effectiveness and safety of moxibustion in patients with prehypertension or hypertension. Methods: Forty-five subjects with prehypertension or stage I hypertension were randomized into three groups: moxibustion treatment group A (2 sessions/week for 4 weeks), moxibustion treatment group B (3 sessions/week for 4 weeks), and control group (nontreated group). The primary outcome measure was the change in blood pressure after 4 weeks of treatment. Safety was assessed at every visit. Results: There were no significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) among three groups after 4 weeks of treatment (p = 0.4798 and p = 0.3252, respectively). In treatment group B, there was a significant decrease in SBP and DBP from baseline to 4 weeks of treatment (mean difference (MD) −9.55; p = 0.0225, MD −7.55; p = 0.0098, respectively). There were no significant differences among groups in secondary outcome measures after 4 weeks of treatment. Six adverse events (AEs) in the treatment group A and 12 AEs in the treatment group B occurred related to the moxibustion treatment. Conclusion: In conclusion, the results of this study show that moxibustion (3 sessions/week for 4 weeks) might lower blood pressure in patients with prehypertension or stage I hypertension and treatment frequency might affect effectiveness of moxibustion in BP regulation. Further randomized controlled trials with a large sample size on prehypertension and hypertension should be conducted. Trial registration: This study was registered with the ‘Clinical Research Information Service (CRIS)’, Republic of Korea (KCT0000469), and the protocol for this study was presented orally at the 15th International Council of Medical Acupuncture and Related Techniques (ICMART) in Athens, 25–27 May 2012.

Cervical varix is rare and can develop due to various conditions in pregnancy. Most cases of cervical varix during pregnancy are diagnosed in the second or third trimester and are usually associated with abnormal placental location, such as placenta previa or low-lying placenta. A 23-year-old woman with cervical varix bleeding visited our institution at 8 weeks of gestation. This case report describes cervical varix bleeding that developed into a venous thrombus in the first trimester. Ultrasonography with color Doppler and magnetic resonance imaging could be helpful in diagnosis.

Background Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines.Methods Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by 51Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. FcγRIIIa (CD16a)-V158F genotyping was performed for healthy donors.Results We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype.Conclusion These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs.

The biological carbon pump in the southwestern East Sea (Japan Sea, EJS hereafter) was investigated based on examination of sinking particulate matter samples intercepted by bottom-tethered sediment traps deployed on a mooring at three depths (500, 1000, and 2000 m) between 2011 and 2017. The total particle flux increased as the sampling depth increased, while particulate organic carbon (POC) flux was greatest at 500 m. The lithogenic material content was high at all depths, and accounted for an average of ∼42% of the particulate matter. The total particle flux at all sampling depths consistently shifted toward much higher values in 2014–2016. During this period, the POC flux at 500 m increased by 32% while net primary production (NPP) increased only slightly. Consequently, the POC flux/NPP ratio increased significantly, indicating greater biological pump efficiency than in earlier years of the study. The flux of lithogenic material derived primarily from sediment resuspension was much greater at 500 m in 2014−2016 compared with previous years, implying its potential role as a ballast mineral in enhancing particle export and transfer to the deep sea interior. The radiocarbon isotope ratio of POC was higher, and the excess Mn content values were lower at 500 m in 2014–2016, suggesting that the resuspended sediment at 500 m likely originated from a shallow region during this period, and differed in provenance from the lithogenic material intercepted at 2000 m. The period of enhanced particle flux coincided with the 2015/16 El Niño and a mesoscale warm (anticyclonic) eddy that persisted for 2 years in the study region. The East Korean Warm Current and the eddy may have facilitated the transport of resuspended particles entrained in the Korea Strait and/or the western shelf and upper slope of the basin to the study site.

Although gravid uterine incarceration is typically diagnosed during the early second trimester, we encountered two unusual cases in early pregnancy. A 34-year-old multiparous woman with adenomyosis presented at 7 + 2 weeks of gestation with increased urinary frequency and a sensation of incomplete bladder emptying. The uterine incarceration was successfully reduced by manual reduction and pessary insertion, and she delivered a normal infant at term. In the second case, a 31-year-old nulliparous woman with a large myoma complained of dysuria, acute urinary retention, and intense back pain at 6 weeks of gestation. Manual reduction was successful in the knee-chest position. Subsequent pessary insertion failed; however, a slight reduction in pain was achieved. After a week, the fetus spontaneously aborted. In summary, gravid uterine incarceration is a rare but potentially fatal condition for the fetus, and a suspicion of this condition in patients with urinary symptoms, especially urinary retention and pelvic pain, is important in the early gestation period.

Background: Deqi is a term describing a special state of the human body, which is ready to cure itself through acupuncture stimulation and is believed to be a key factor in acupuncture treatment. However, knowledge about deqi remains subjective. Therefore, in this study, we aimed to determine the factors related to deqi generation based on present studies to promote the progression of deqi research. Methods: A term frequency–inverse document frequency (Tf-idf) was used to extract key elements from the abstracts of 148 articles searched from Pubmed, and the network structure between key elements was analyzed. Results: A total of 37 items were extracted from the abstracts. Each item was categorized into one of three groups (acupuncture-related sensation, interventions or organ/mechanism). Acupuncture-related sensation was studied by comparing the items in the interventions group with the organ/mechanism group. Key elements related to deqi generation included muscles from the organ/mechanism group and intensity, depth and pressure from the interventions group. Items that belonged to the acupuncture-related sensation group were divided into two clusters: one cluster consisted of pain, tingling, aching, soreness, heaviness, fullness and numbness; the other included warm, cold and dull. Conclusion: We could find out that the trend of deqi was leaning towards the interventions group, which related to the generation of deqi; thus, authors concluded that the mechanism studies, which are aimed to investigate why deqi is generated or what kind of meanings it has, are needed for evolution of acupuncture theory and application of the brand new technologies and related devices. Keywords: Deqi, Text mining, Network analysis, Acupuncture, Trend

Background Physical function may influence perioperative outcomes of lung transplantation. We investigated the feasibility of a pulmonary rehabilitation program initiated in the immediate postoperative period at an intensive care unit (ICU) for patients who underwent lung transplantation. Methods We retrospectively evaluated 22 patients who received pulmonary rehabilitation initiated in the ICU within 2 weeks after lung transplantation at our institution from March 2015 to February 2016. Levels of physical function were graded at the start of pulmonary rehabilitation and then weekly throughout rehabilitation according to criteria from our institutional pulmonary rehabilitation program: grade 1, bedside (G1); grade 2, dangling (G2); grade 3, standing (G3); and grade IV, gait (G4). Results The median age of patients was 53 years (range, 25 to 73 years). Fourteen patients (64%) were males. The initial level of physical function was G1 in nine patients, G2 in seven patients, G3 in four patients, and G4 in two patients. Patients started pulmonary rehabilitation at a median of 7.5 days (range, 1 to 29 days) after lung transplantation. We did not observe any rehabilitation-related complications during follow-up. The final level of physical function was G1 in six patients, G3 in two patients, and G4 in 14 patients. Fourteen of the 22 patients were able to walk with or without assistance, and 13 of them maintained G4 until discharge; the eight remaining patients never achieved G4. Conclusions Our results suggest the feasibility of early pulmonary rehabilitation initiated in the ICU within a few days after lung transplantation.

Abstract Background Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. Method We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. Result A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R0 value in Saudi Arabia was

Background: Hypertension is a major cause of cardiovascular disease and associated mortality, and postmenopausal women are at a high risk of hypertension. We aim to investigate the hypotensive effect and safety of acupuncture, focusing on postmenopausal women with prehypertension and stage 1 hypertension. In addition, we aim to investigate whether the effect of acupuncture treatment differed, depending on Sasang Constitution and cold–heat pattern. Methods: This study is designed as an intervention cohort study. Two hundred postmenopausal women aged

Background and Objectives: To examine the effect of maternal breastfeeding on the subsequent risk of diabetes in parous Korean women aged >50 years. Materials and Methods: A total of 14,433 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) were included. The subjects were divided into three groups: normal, impaired fasting glucose, and diabetes. The adjusted odds ratios (ORs) for impaired fasting glucose (IFG) and diabetes were assessed using multivariate logistic regression. Results: A total of 2301 (15.94%) women were classified as having diabetes, and 3670 (25.43%) women were classified as having impaired fasting glucose. Breastfeeding was associated with an OR for diabetes of 0.76 (95% confidence interval (CI): 0.61, 0.95) compared with non-breastfeeding after adjustment for possible confounders in the multivariable logistic regression analysis. Breastfeeding for 13–24 months was associated with an OR of 0.68 (95% CI, 0.5, 0.91), and breastfeeding for 25–36 months was associated with an OR of 0.68 (95% CI, 0.52, 0.87) for diabetes compared with breastfeeding for

Background: Spontaneous hepatic rupture associated with the syndrome characterized by hemolysis, elevated liver enzymes, and a low platelet count (HELLP syndrome) is a rare and life-threatening condition, and only a few cases regarding the management of this condition through transcatheter arterial embolization (TAE) have been previously reported. Case summary: Herein, we report a case involving a 35-year-old pregnant woman who presented at 28 weeks of gestation with right upper quadrant pain, hypotension, and elevated levels of liver enzymes. Transabdominal ultrasound revealed fetal death. She required an emergency cesarean section, and hepatic rupture was identified after the fetus had been delivered. Hepatic packing and TAE were performed. The postprocedural course was uneventful, and the patient was discharged 14 days after she had been admitted to our hospital. Conclusions: Spontaneous hepatic rupture associated with HELLP syndrome is a very serious condition that requires prompt and decisive management. The high maternal and fetal mortality rates associated with this condition can be reduced through early accurate diagnosis and adequate management. The findings in the reported case indicate that TAE may be an attractive alternative to surgery for the management of spontaneous hepatic rupture associated with HELLP syndrome.

Background/Aims: The eradication rate of Helicobacter pylori (H. pylori) has been decreasing recently in Korea due to antibiotics resistance. The aim of this study was to investigate the trend of eradication rate and clinical factors affecting the eradication rate of H. pylori in the last 10 years in west Gyeonggi-do, Korea. Methods: The trends of eradication rate of H. pylori, gender, age, concomitant mediations, and clinical factors were retrospectively evaluated in patients with H. pylori infection between 2006 and 2015 (n=2,485). Results: The overall H. pylori eradication rate for the standard triple therapy was 82.5%. The annual eradication rates from 2006 to 2015 were 90%, 77.9%, 75.8%, 83.2%, 85.6%, 90.1%, 81.3%, 81.1%, 78.7%, and 78.8%, respectively, showing a significant decrement during the last five years (p〈 0.001). Higher eradication rate was observed in males than in females (p〈 0.001). Esomeprazole showed a higher eradication rate compared with pantoprazole between 2006 and 2010 (p〈 0.022). Age and the use of probiotics and mucosal protective agents played no significant role in the H. pylori eradication rate. The overall eradication rate for bismuth-based quadruple therapy was 94.4%. Conclusions: The eradication rate of H. pylori over the last 10 years for first-line therapy ranged from 75.8 to 90.1%; the eradication rate for triple therapy has declined. However, the eradication rate for quadruple therapy has remained unchanged over the last 10 years.

Endothelial dysfunction has been linked to vascular inflammation and foam cell formation but the underlying mechanisms still remain unclear. We sought to define the factors inducing inflammation and smooth muscle foam cell formation under endothelial dysfunction using endothelial nitric oxide synthase (eNOS)-deficient mice. Vascular smooth muscle cells (VSMCs) from eNOS-deficient mice displayed increased expression of macrophage-related genes and elevated lipid uptake. Neuropeptide Y (NPY) was upregulated in the aorta from the eNOS-deficient mice and promoted macrophage chemotaxis toward VSMCs while enhancing the activity of matrix metalloproteinase-3. Notably, NPY induced lipid uptake in VSMCs, facilitating smooth muscle foam cell formation, in association with enhanced expression of genes related to modified low-density lipoprotein uptake and macrophages. NPY was augmented by inflammatory pentraxin 3 (PTX3) in VSMCs. PTX3 enhanced macrophage migratory capacity through the NPY/neuropeptide Y receptor axis and this effect was attenuated by pharmacological inhibition with a receptor-specific antagonist. These observations suggest that endothelial dysfunction leads to the elevation of NPY that amplifies vascular inflammation by increasing inflammatory cell chemotaxis and triggers smooth muscle foam cell formation.

Background and Objectives: Vaginitis causes vulvovaginal symptoms, including itching, irritation, vaginal discharge, burning, or foul odor. It is one of the most common diseases encountered in gynecologic practice. Hypoestrogenism due to menopause has a considerable negative effect on vaginal health and leads to changes in the vaginal pH and vaginal microflora, which are related to a change in the causes and microorganisms of vaginitis. Thus the aim here was to investigate the prevalence of pathogens and other microorganisms in premenopausal and postmenopausal women with vulvovaginal symptoms, using an STD 12-Multiplex real-time PCR test and routine culture of vaginal discharge. Materials and Methods: From January 2018 to December 2019, records of patients diagnosed with vaginitis at Changwon Gyeongsang National University Hospital were retrospectively reviewed. The premenopausal and postmenopausal subjects were categorized into Group A and Group B, respectively. and the data of symptoms, general characteristics, and results of both STD 12-Multiplex real-time PCR test and routine culture of vaginal discharge were retrieved. Results: On the STD 12-Multiplex real-time PCR test, Gardnerella vaginalis was the most common microorganism in both groups. Ureaplasma parvum was the second most common one, followed by Candida speceies. On the routine culture of vaginal discharge, Escherichia coli was the most common aerobic bacterial microorganism in both groups, followed by Streptococcus agalactiae (Group B Streptococcus, GBS). There was no significant difference between the two groups. Pathogens and other microorganisms of patients with vulvovaginal symptoms that showed a statistically significant difference between the two groups were Ureaplasa parvum, Ureaplasma urealyticulum, Trichomonas vaginalis, and Staphylococcus aureus. Conclusion: In this study, the prevalence of pathogens and other microorganisms in menopausal women with vulvovaginal symptoms did not show a significant difference from premenopausal women. Therefore, management strategies for patients with vulvovaginal symptoms should be developed through accurate diagnosis using appropriate diagnostic methods.

Background and Objectives: This study aimed to investigate whether mild fetal tricuspid regurgitation (TR) at 11+ 0 to 13+ 6 weeks of gestation affects perinatal outcomes. Since fetal right ventricular load is associated with placental resistance, we hypothesized that fetal mild TR would be associated with perinatal outcomes as a consequence of abnormal placentation. Materials and Methods: We retrospectively evaluated 435 women with first-trimester scan data. Blood flow across the tricuspid valve was examined in singleton pregnancies between 11+ 0 and 13+ 6 weeks of gestation. Women were categorized according to the presence or absence of fetal mild TR, and the maternal and pregnancy characteristics and perinatal outcomes were compared. Multiple linear and logistic regression analyses were conducted to identify independent predictors of perinatal outcome. Results: In the group with mild TR, there were more cases of borderline amniotic fluid index, including oligohydramnios (p = 0.031), and gestational age- and sex-specific birth weights were lower (p = 0.012). There were no significant differences in other perinatal outcomes, including preeclampsia, gestational hypertension and small for gestational age. Gestational diabetes (adjusted odds ratio (OR) 0.514, 95% confidence interval (CI) 0.312–0.947) and fetal mild TR (adjusted OR 1.602, 95% CI 1.080–2.384) were identified as factors associated with below borderline amniotic fluid index before birth. The factors that affected gestational age and sex-specific birth weight were also gestational diabetes (adjusted beta coefficient 9.673, p = 0.008) and the presence of fetal mild TR (adjusted beta coefficient −6.593, p = 0.007). Conclusions: Mild fetal TR observed in the first trimester is negatively associated with fetal growth and the amniotic fluid index at term but not with other adverse pregnancy or perinatal outcomes due to abnormal placentation.

The detection and removal of erroneous pixels is a critical pre-processing step in producing chlorophyll-a (chl-a) concentration values to adequately understand the bio-physical oceanic process using optical satellite data. Geostationary Ocean Color Imager (GOCI) chl-a images revealed that numerous speckle noises with enormously high and low values were randomly scattered throughout the seas around the Korean Peninsula as well as in the Northwest Pacific. Most of the previous methods used to remove abnormal chl-a concentrations have focused on inhomogeneity in spatial features, which still frequently produce problematic values. Herein, a scheme was developed to detect and eliminate chl-a speckles as well as erroneous pixels near the boundary of clouds; for the purpose, a deep neural network (DNN) algorithm was applied to a large-sized GOCI database from the 6-year period of 2012–2017. The input data of the proposed DNN model were composed of the GOCI level-2 remote-sensing reflectance of each band, chl-a concentration image, median filtered, and monthly climatology chl-a image. The quality of the individual images as well as the monthly composites of chl-a data was improved remarkably after the DNN speckle-removal procedure. The quantitative analyses showed that the DNN algorithm achieved high classification accuracy with regard to the detection of error pixels with both very high and very low chl-a values, and better performance compared to the general arithmetic algorithms of the median filter and threshold scheme. This implies that the implemented method can be useful for investigating not only the short-term variations based on hourly chl-a data but also long-term variabilities with composite products of the GOCI chl-a concentration over the span of a decade.

Obesity is accompanied by chronic systemic inflammation characterized by macrophage infiltration of obese tissues, an elevated plasma level of inflammatory substances, and excessive accumulation of lipids. The pro-inflammatory factor pentraxin 3 (PTX3) is also elevated in obese tissues, suggesting its potential role in adipogenesis. We found by analyzing murine preadipocyte 3T3-L1 cells, and human adipocytes derived from mesenchymal stem cells, which locally elevated PTX3 in obese adipose tissue augments adipocyte differentiation and subsequent lipid accumulation. This occurs via the upregulation of adipogenesis-related transcription factors. PTX3 enhanced lipid accumulation in murine 3T3-L1 cells by upregulating the expression of neuropeptide Y (NPY)/NPY receptor (NPYR) expression in preadipocytes. Pharmacological inhibition by NPYR antagonists abolished these effects. NPY also promoted the production of reactive oxygen species (ROS), a known trigger of adipogenesis. NPYR antagonists as well as antioxidant N-acetylcysteine showed anti-adipogenic effects by reducing the ROS levels, indicating that PTX3 mediates adipogenesis through NPY-dependent ROS production. These findings suggest that PTX3 plays a key role in the development of obesity by enhancing adipocyte differentiation and lipid synthesis via NPY/NPYR signaling. These observations provide a mechanistic explanation for the adipogenesis mediated by PTX3.

D-allulose, a C-3 epimer of D-fructose, is a rare monosaccharide used as a food ingredient or a sweetener. In the present study, the in vitro metabolic stability of D-allulose was examined in biorelevant media, that is, simulated gastric fluid (SGF) and fasted state simulated intestinal fluid (FaSSIF) containing digestive enzymes, and in cryopreserved human and rat hepatocytes. The hepatocyte metabolic stabilities of D-allulose were also investigated and compared with those of fructose and erythritol (a sugar-alcohol with no calorific value). D-allulose was highly stable in SGF (97.8% remained after 60 min) and in FaSSIF (101.3% remained after 240 min), indicating it is neither pH-labile nor degraded in the gastrointestinal tract. D-allulose also exhibited high levels of stability in human and rat hepatocytes (94.5−96.8% remained after 240 min), whereas fructose was rapidly metabolized (43.1−52.6% remained), which suggested these two epimers are metabolized in completely different ways in the liver. The effects of D-allulose on glucose and fructose levels were negligible in hepatocytes. Erythritol was stable in human and rat hepatocytes (102.1−102.9% remained after 240 min). Intravenous pharmacokinetic studies in rats showed D-allulose was eliminated with a mean half-life of 72.2 min and a systemic clearance of 15.8 mL/min/kg. Taken together, our results indicate that D-allulose is not metabolized in the liver, and thus, unlikely to contribute to hepatic energy production.

To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening.We used Portuguese national clinical and economic data to conduct a model-based assessment.We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness.One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively.One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal's challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.

The World Health Organization (WHO) has called for the "virtual elimination" of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe.We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A" (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B" (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%.Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination" of pediatric HIV in Zimbabwe. Please see later in the article for the Editors' Summary.

Common buckwheat (Fagopyrum esculentum Moench.) is one of the most important orphan crops worldwide. Various research efforts have been done to improve cultivation methods to enhance important agronomic traits such as productivity and biotic/abiotic resistance. One important aspect is the seed trait, which has not been extensively studied due to the time-consuming and tedious nature of its examination. Despite this, understanding seed traits is crucial for meeting consumer needs and optimizing crop yields. Therefore, the aim of the study is to investigate the inheritance of common buckwheat seed traits--such as shape, size, and coat color--using an image-based approach. This method allows for the analysis of a large number of seeds with a level of accuracy and precision that was previously unattainable. The results indicate that seed coat color is inherited maternally. Notably, the parameters in size had substantial increases acting like overdominance. The number of seeds that were harvested from F1s of each cross differed a lot depending on the cross combinations and pin/thrum type. In addition, seed size had large reduction in F1s from the different seed-sized parents, especially in thrum type. These may show that there could be cross barriers. The results revealed trends of maternal inheritance for seed shape and coat color in buckwheat, an area that has not been extensively studied. These findings could support buckwheat breeding efforts, helping to address market needs and food demands in the face of significant climate change. [ABSTRACT FROM AUTHOR]