Vicia faba L. minor) is an important grain legume and is widely used as food and feed. It is traditionally used as a spring crop in Central European cropping systems. There is increasing interest in winter faba bean due to a higher yield potential, but limited knowledge of nitrogen (N) yields and nitrogen fixation (NFIX) exists. Therefore, the purpose of this study was to compare N concentrations, N yield of plant fractions, soil mineral N (SMN) and SMN sparing in the soil after harvest, NFIX and N balance of two winter faba bean varieties (Diva and Hiverna) to those of a spring faba bean (Alexia) using two seeding rates (25 versus 50 germinable seeds m−2) in a two-year field experiment under Pannonian climate conditions in eastern Austria. The winter faba bean varieties had higher N yields and NFIX, not only due to higher biomass yields, but also due to higher N concentrations and a higher percentage of N derived from atmosphere in the biomass. Conversely, the soil mineral N after harvest was lower compared to the spring faba bean. All treatments had a negative N balance due to higher grain N yield than NFIX. Winter faba beans left higher amounts of biologically-fixed N in residues for the subsequent crop, whereas spring faba bean left more SMN. Winter faba bean varieties obtained good results with both seeding rates, whereas the grain yield and the grain N yield of Alexia tended to higher with the higher seeding rate.Faba bean ( Faba bean is a protein-rich grain legume which is widely used as food and feed for monogastric animals and ruminants. It is well adapted to most climatic areas of Europe . HoweverFurther, climate change is expected to result in higher temperatures all year round and a lower total annual amount of precipitation in Central Europe, but may also cause more precipitation in winter and early spring and less precipitation in summer. This will make the cultivation of spring crops much more challenging in Central Europe . FosteriFIX) of atmospheric N through symbiosis with N-fixing soil bacteria, from which they can satisfy the bulk of their N demand [FIX plays a critical role in crop production, providing almost 20% of worldwide needed N for grain and oilseed crop production [Grain legumes strongly contribute to the diversification, sustainability and long-term productivity of agricultural systems, due to the biological nitrogen fixation , have already been reported [GRAIN) of winter faba bean varieties were over all seeding ratios and years 1.71-fold (Diva) or 1.33-fold (Hiverna) higher compared to the spring faba bean Alexia. Winter faba bean varieties had further higher values for above-ground dry matter yield, stem density, number of stems plant−1, thousand kernel weight (TKW) and grain yield pod−1. Seeding rates (25 versus 50 germinable seeds m−2) did not affect the YGRAIN of Diva, but the YGRAIN of Hiverna was higher at the lower seeding rate, while that of Alexia tended to be higher at the higher rate. The higher seeding rate resulted in a higher plant density and stem density but reduced the number of stems plant−1 (of winter faba bean varieties) and the number of pods plant−1.Plant density is one of several agronomical practices that need to be addressed for the improvement of faba bean production in European cropping systems . Optimum 2 years . Howeverants m−2 . For thereported : the graFIX of winter faba bean in general and particularly of optimal seeding rates under Central European growing conditions. Therefore, the aim of this study was to compare winter and spring faba bean in eastern Austria in order to gain knowledge on N uptake and NFIX under contrasting sowing dates as affected by seeding rates.Limited knowledge is available for N uptake and NCaCl2 = 7.6, silty loam, 2.2–2.3% organic matter). Soil mineral nitrate (NO3-N) in 0–0.9 m depth at sowing was at 21.7 g m−2 (17 October 2013), 13.0 g m−2 (13 October 2014), 18.4 g m−2 (4 March 2014) and 11.2 g m−2 (16 March 2015).The experiment was performed at the experimental farm Groß-Enzersdorf of the University of Natural Resources and Life Sciences Vienna (BOKU) in Raasdorf  on a chernozem soil of alluvial origin which is rich in calcareous sediments . The temperature in the vegetation period of winter crops (October to July) in both years was above the long-term average and the precipitation was, in the first experimental year, above and, in the second, below the long-term average. For monthly means, see Neugschwandtner et al. [3–2012. T−2. Winter wheat Xenos was grown as a reference crop for NFIX, with 300 germinable seeds m−2. Crops were harvested from end of June to mid-July. No fertilization was performed. The experiment was performed in the years 2013/14 and 2014/15. Detailed information on varieties, weed and pest control, seeding and harvest dates is given in Neugschwandtner et al. [Winter faba beans varieties Diva and Hiverna were sown in October and the spring faba bean variety Alexia in March. Seeding rates were 25 or 50 germinable seeds mr et al. .GRAIN), pod walls (NCPW) and stems and leaves (NCSL) were determined as an average of duplicate samples of about 50 mg each, via the Dumas combustion method [GRAIN) on the above-ground dry matter NY. The N utilization efficiency for the production of AGDM (NUtEAGDM) or grain (NUtEGRAIN) was calculated according to Sinebo et al. [AGDM or YGRAIN are the yields of AGDM or grain and NYAGDM is the N yield of the above-ground dry matter (AGDM).The N concentrations of grain  for 1 h using an overhead shaker [3-N) was determined photometrically .Soil sampling after harvest was performed to a depth of 0.9 m with soil probes . Samples were further divided into three layers: 0–0.3, 0.3–0.6 and 0.6–0.9 m. Soil samples were extracted with 0.0125 M CaCld shaker . The resFIX) at harvest was calculated by comparing the differences of the NYAGDM (∆ NYAGDM) and the SMN depletion (SMN sparing) in the soil (0–0.9 m) between the legume and non-legume reference crop (winter wheat), using the extended difference method [AGDM-Leg and NYAGDM-Ref are the quantities of N in the above-ground dry matter and SMNLeg and SMNRef are the amounts of SMN of the legume and the reference crop. All values are in g m−2. The lower removal of SMN by the legume compared to a cereal during crop growth is termed as ‘nitrogen sparing’ [AGDM-Ref was 11.7 (2013/14) or 13.0 (2014/15) g m−2 and the SMNRef was 3.33 (2013/14) or 0.14 (2014/15) g m−2. The symbiotically fixed N per unit area (Ne method  as follosparing’ . The NYAAGDM derived from atmospheric fixation (Ndfa) in the AGDM was calculated according to Urbatzka et al. [The percentage of the NYa et al.  as folloFIX per unit of AGDM (NFIX-AGDM) of faba bean at harvest was calculated as follows:The NFIX and N removal of the grain according to Wichmann et al. [The N balance was calculated as the difference between Nn et al.  as follo2 (10 × 1.5 m). Analysis of variance using a nested design with replications nested within years was performed with SAS version 9.2. Means were separated by least significant differences (LSD) when the F-test indicated factorial effects at the significance level of p < 0.05.The experimental setup was a randomized complete block design with 4 replications and an individual plot area of 15 mGRAIN: 272 g m−2, yield of pod walls (YPW): 59 g m−2, yield of stems and leaves (YSL): 377 g m−2.The mean biomass yields over all varieties, seeding rates and years were as follows: YGRAIN ranked among varieties at different seeding rates as follows: 25—Diva > Hiverna > Alexia; 50—Diva ≥ Hiverna ≥ Alexia. The YGRAIN of Diva and Hiverna were 1.68-fold or 1.32-fold higher compared to Alexia . Diva had a higher YGRAIN at 25 when compared with 50 seeds m−2; Alexia tended to be higher with 50 than with 25 seeds m−2, whereas Hiverna was not affected by seeding rate. The YGRAIN did not differ between the years : 0.83 g m−2, N yield of stems and leaves (NYSL): 3.59 g m−2, N yield of total residues (NYTR): 4.42 g m−2 and NHI: 73.8%.The mean values for NC and NY over all varieties, seeding rates and years were for NCGRAIN was ranked among varieties as follows: 2013/14—Diva > Alexia, Hiverna; 2014/15—Diva > Hiverna > Alexia, with a higher concentration for Diva in 2014/15 than in 2013/14 and no difference between years for Hiverna and Alexia. The NCGRAIN of Diva and Hiverna were 1.08-fold or 1.04-fold higher compared to Alexia  (The NCd years) . PW of Diva was higher than of that of the other varieties in 2014/15 than in 2013/14. No difference between varieties occurred in 2013/14 and Hiverna and Alexia had similar concentrations in both years   . GRAIN, NCPW and NCSL . No significant differences occurred between seeding rates and years, but the NYGRAIN showed a tendency to be higher in 2014/15 than in 2013/14 . For Alexia, both the NYAGDM  and the NYGRAIN  also tended to be higher at 50 than at 25 seeds m−2, with lower differences between seeding rates for Diva and Hiverna  (The NYng rates . The YSLd years) .The NHI was ranked as follows: 2013/14—Diva, Alexia > Hiverna; 2014/15—Diva ≥ Alexia ≥ Hiverna. It was higher for all three varieties in 2014/15 than in 2013/14, with larger differences for Hiverna. The NHI did not differ between seeding rates .GRAIN on the single plant level over all varieties, seeding rates and years were as follows: NYGRAIN plant−1: 407 mg, NYGRAIN stem−1: 214 mg, NYGRAIN pod−1: 54.7 mg and NYGRAIN grain−1: 16.9 mg. The mean NYGRAIN plant−1 among varieties was generally ranked as follows: Diva > Hiverna > Alexia. Diva and Hiverna had a higher NYGRAIN plant−1 at 25 than at 50 seeds m−2, whereas no difference between seeding rates was found for Diva .The NYAGDM: 42.0 g g−1 and for NUtEGRAIN: 15.9 g g−1. The mean NUtE over all varieties, seeding rates and years was for NUtEAGDM among varieties was ranked as follows: 2013/14—Hiverna > Diva ≥ Alexia; 2014/15—Hiverna, Alexia > Diva. Diva had a higher NUtEAGDM in 2013/14 and Alexia in 2014/15 when compared to the other year, while no difference between years was observed for Hiverna .The NUtEand Diva . The NUt−2, ∆ NYAGDM: 4.78 g m−2, SMN sparing: 3.96 g m−2, NFIX: 8.74 g m−2, Ndfa: 46.7%, NFIX-AGDM: 11.7 mg g−1 and N balance: −3.96 g m−2.The mean values over all varieties, seeding rates and years for SMN at harvest in a soil depth of 0–0.9 m were 5.70 g mThe SMN was ranked as follows: variety—Alexia > Diva, Hiverna; year—2013/14 > 2014/15; seeding rate did not affect SMN . AGDM was ranked as follows: variety—Diva, Hiverna > Alexia; year—2014/15 > 2013/14. The ∆ NYAGDM of Alexia tended to be higher at 50 compared to 25 seeds m−2, with no difference for Diva and Hiverna   .The SMN sparing ranked among varieties as follows: Alexia > Diva, Hiverna. For Alexia it was 1.47-fold or 1.68-fold higher compared to Diva and Hiverna. It did not differ between seeding rates and years . FIX was ranked among varieties as follows: Diva, Hiverna > Alexia. For Diva and Hiverna, it was 2.47-fold or 2.00-fold higher compared to Alexia. The NFIX did not differ between seeding rates. It tended to be higher in 2013/14 than in 2014/15   .−2 . It was 1.39-fold higher in 2013/14 than in 2014/15   .GRAIN and NYTR than the spring faba bean. Details are shown in Neugschwandtner et al. [GRAIN results from the higher crop plasticity in the formation of yield components, which becomes more evident with a longer growing period and with earlier seeding [Winter faba beans had generally higher NYr et al. . A highe seeding ; this ca seeding . Neverth seeding . Low win seeding .GRAIN and NCPW, but not NCSL, were higher in winter faba beans than in the spring faba bean. Seeding rate did not affect NC in plant, although a higher protein concentration was observed at a higher seeding rate for soybean [NC soybean ,21.GRAIN and NCGRAIN were higher in winter faba beans compared to the spring faba bean, the NYGRAIN was also considerably higher. The highest NYGRAIN was obtained with 16.5 g m−2 by Diva, thereby having a 1.80-fold higher value than Alexia. Under much colder and wetter conditions in south-western Germany, a NYGRAIN of 22 g m−2 was achieved with spring faba bean [Just as both Yaba bean . Faba beTR of winter faba beans, despite lower NCPW, resulted in higher NYTR compared to the spring faba bean. Similar to our observations, Aufhammer et al. [GRAIN and NYTR, concluding that conditions which enable the formation of a high YGRAIN also contribute significantly to a higher NYTR. Based on results of our study, this optimum condition would be seeding winter faba bean and not spring faba bean. The highest NYTR was observed for Hiverna, with 6.33 g m−2, which was below values reported for spring faba bean grown in south-western Germany, with values ranging from 7 to 17 g m−2 [TR and thereby resulting positive pre-crop effects might be even higher. Higher NCGRAIN but lower NCPW resulted in a higher NHI compared to the harvest index (HI) for winter faba bean, whereas the HI and the NHI for the spring faba bean was in a similar range .GRAIN plant−1 was ranked as follows: Diva > Hiverna > Alexia. Considering additionally the higher NCGRAIN of winter faba bean, the NYGRAIN plant−1 was higher in winter faba beans than in the spring faba bean. Hiverna had the highest number of stems plant−1; consequently, the NYGRAIN shoot−1 was lower than that of Diva and Alexia. The higher YGRAIN pod−1 of winter faba beans resulted from the higher TKW and a higher number of grains pod−1 (except for Hiverna in one year). Considering additionally the higher NCGRAIN of winter faba beans, the NYGRAIN pod−1 of winter faba beans was almost two times higher than that of Alexia. The considerably higher NYGRAIN grain−1 of Diva and Hiverna compared to Alexia resulted from both the higher NCGRAIN and the higher TKW.A yield component analysis for this experiment (cf. ) showed AGDM among varieties but, due to the high residue yields and the low NHI, the lowest NUtEGRAIN, whereas those of Diva and Alexia did not differ. However, autumn-sowing of facultative wheat resulted in a higher NUtEAGDM than spring-sowing [GRAIN was higher in the drier vegetation period 2014/15. Contrary to that, the NUtEGRAIN of barley, oat and pea were severely decreased by drought [GRAIN was higher for all varieties at the lower seeding rate. Interference during grain formation may cause a lower NUtE, as reported in triticale–faba bean intercrops [The NUtE gives the yield per unit N in the above-ground dry matter; thus, higher values show that more biomass could be produced with the N which was taken up. Hiverna had the highest NUtEg-sowing . The NUt drought . In one tercrops  and oat–tercrops . Furthertercrops ,43. The tercrops .AGDM compared to winter faba bean but also a lower rooting density, this might be the reason for both the higher SMN and SMN sparing.SMN and SMN sparing were higher in Alexia than in Diva and Hiverna. A higher residual nitrate content in the soil at harvest of faba bean compared to oat was attributed to lower rooting density and, thereby, the lower nitrate uptake of faba bean . AssuminFIX of Diva and Hiverna were with 11.83 or 9.59 g m−2 considerably higher than that of Alexia (4.80 g m−2). At the same location, values for NFIX for winter faba bean of 6.3 g m−2 due to low overwintering and of 21.9 g m−2 under optimum conditions have been reported [FIX for spring faba bean and spring pea in Bavaria (Germany) ranged between 16.5 and 24.0 g m−2 for spring faba bean and between 21.5 and 24.6 g m−2 for spring pea [The mean value of Nreported . Values ring pea .FIX of Diva and Hiverna resulted mainly from their higher ∆ NYAGDM, which for each variety was more than three times higher than their SMN sparing. The positive value of NFIX of Alexia, however, resulted solely from SMN sparing, as its ∆ NYAGDM was negative, with a lower NYAGDM than the reference crop winter wheat. The higher NPositive yield effects of legumes on subsequent crops have been attributed to the release of biologically-fixed N from residues and the SMN sparing of legumes ,47. ConsFIX of winter faba bean and winter pea were enhanced by the increased temperature during their vegetative growth in winter, whereas the NFIX of spring pea was reduced by an above-optimal temperature during its vegetative growth in spring [FIX in 2014/15 compared to 2013/14 might be explained by less rainfall during the vegetation period, as water stress is the overriding factor for driving yield and NFIX of faba bean [In a climate change simulation study for conditions in south-western France, the simulated Nn spring . The lowThe highest value for Ndfa was seen in Diva, at 56.6%, and the lowest in Alexia, at 34.1%. Zapata et al.  even repFIX-AGDM was 11.7 mg g−1, with higher values for Diva than for Alexia. The NFIX-AGDM for spring pea grown at the same location in pure stands and intercrops with oat was 22.9 mg g−1, as the NFIX was with 18.51 g m−2, also more than two times higher than the mean value in our study [FIX for winter pea than for winter faba bean under Pannonian climate conditions has already been reported [The mean Nur study . Also, areported .FIX was lower than NYGRAIN. However, the negative N balance of Diva and Alexia was only half that of the reference crop winter wheat. Also, the N balance of spring faba bean grown in northern Germany was negative at −5.7 g m−2, whereas that of spring pea was positive at 1.9 g g m−2 [The N balance for all varieties had negative values, as N g g m−2 . Senarat g g m−2  also obsGRAIN tended to be higher (n. s.) while NFIX was lower.Hiverna had the lowest negative N balance (n. s.) due to having the lowest NHI. The negative N balance increases with a higher harvest index and a higher N harvest index, as more N is transferred from the field . The N bFIX, due to not only higher biomass yields, but also a higher NCGRAIN and a higher Ndfa. The positive pre-crop effect of winter faba bean might be higher because more N is left in the field, mainly in the residues, though spring faba bean has a higher SMN sparing. Winter faba bean can be sown with a low seeding rate of 25 germinable seeds m−2, whereas the seeding rate of 50 germinable seeds m−2 for the spring faba bean results in a higher NYGRAIN. Among winter faba bean varieties, Diva had a higher YGRAIN, NCGRAIN, NYGRAIN, NHI and NFIX, whereas Hiverna had a higher YSL, NYTR and a less negative N balance.Winter faba bean is superior to spring faba bean in achieving high NY and high N


We included 35 patients . Baseline mean ± SD SPD was 5008 ± 4234, with no differences between IPF and non-IPF ILD. At baseline, cough was reported by 94.3% patients (mean ± SD VAScough 3.3 ± 2.6). Compared to non-IPF ILD, patients with IPF had significantly higher burden of cough (p = 0.020), and experienced a greater increase in cough over six months (p = 0.009). Patients who died or underwent lung transplantation (n = 5), had significantly lower SPD (p = 0.007) and higher VAScough (p = 0.047). Long-term follow up identified VAScough  and SPD  as significant predictors for transplant-free survival. In conclusion, although activity didn’t differ between IPF and non-IPF ILD, cough burden was significantly greater in IPF. SPD and VAScough differed significantly in patients who subsequently experienced disease progression and were associated with long-term transplant-free survival, calling for better acknowledgement of both parameters in disease management.Physical activity limitations and cough are common in patients with interstitial lung disease (ILD), potentially leading to reduced health-related quality of life. We aimed to compare physical activity and cough between patients with subjective, progressive idiopathic pulmonary fibrosis (IPF) and fibrotic non-IPF ILD. In this prospective observational study, wrist accelerometers were worn for seven consecutive days to track steps per day (SPD). Cough was evaluated using a visual analog scale (VAS Fibrotic interstitial lung diseases are severe conditions in which a range of symptoms restrict patients’ everyday lives. Beyond dyspnea and impaired respiratory capacity , other fWe are not aware of studies simultaneously investigating both physical activity and cough in fibrotic ILD, comparing IPF and non-IPF ILD. Therefore, we aimed to characterize the differences in cough and physical activity between patients with IPF and those with non-IPF fibrotic ILD, and to evaluate their relationship with HRQoL.In this prospective observational study, physical activity and cough were assessed in patients with subjective, progressive fibrotic ILD using accelerometers and self-report questionnaires. In our study, the definition of “progressive fibrotic ILD” was defined as any subjective increase in dyspnea and/or physical limitations within the last six months. An acute infection, heart failure, atrial fibrillation or anaemia causing the subjective deterioration was excluded prior to inclusion in the study. Progression did not include worsening of pulmonary function and/or increase of fibrosis on high-resolution computed tomography (HRCT). Patients were recruited between July 2017 and August 2018 in the in- and out-patient unit of the Department of Internal Medicine V of the University of Munich, and were followed for 6 months. The study was conducted in accordance with the amended Declaration of Helsinki and approved by the local ethics committee of the University of Munich, Germany and (UE No. 812-16). All patients provided written informed consent.We included individuals with a consensus diagnosis of fibrotic ILD, including IPF, chronic hypersensitivity pneumonitis, connective tissue disease-related ILD (CTD-ILD), non-specific interstitial pneumonia (NSIP) and unclassifiable pulmonary fibrosis. All diagnoses were made based on multidisciplinary discussion of the diagnosis in accordance with the current international criteria ,13,14. MPatients were followed prospectively until disease progression, or on completion of a follow-up-duration of 6 months. Disease progression was defined as lung transplantation, or death due to respiratory failure. Long-term follow-up was evaluated until 30 April 2023.Each patient was given 30 min dedicated instruction on how to use the wristband accelerometer , which was initialized with personal settings  and then worn on the nondominant wrist for seven consecutive days at baseline. Patients were instructed to follow their daily, normal physical activity level, and only remove the monitors for sleep during nighttime. The activity monitors were only worn for 7 consecutive days at baseline. Data were recorded on the device, which was sent back to the hospital after 7 days, where data were read out and analyzed using the Polar Flowsync software version 2017 and 2018 . Accelerometer data were considered usable for each day if the patient had worn the device for more than 10 h. Recorded activity was categorized as: Lying, sitting, standing, walking, or running. Based on these data, activity time was defined as the sum of standing, walking and running time. In addition, wearing time of the accelerometer, steps per day (SPD) and distance covered (in meters) were recorded and analyzed. Only patients with at least 4 days on which the device was worn for more than 10 h per day during the 7 consecutive days were included in the final analysis.cough) for cough with higher values indicating greater burden of cough [cough has been shown as to be a valid tool assessing cough severity in patients with chronic cough [cough was done at baseline and after 3 and 6 months in the hospital, with patients also requested to fill out a VAScough weekly over 6 months.Patients were instructed to complete a visual analog scale , which was designed as a clinical research tool to study overall health, daily life, and perceived well-being in patients with chronic airways disease , has beecough change over the follow-up period, a linear regression model was used with all available parameters without imputation. Individual VAScough variation was calculated using the coefficient of variation (CoV) of all VAScough values within the first three months. To evaluate long-term effects in the study cohort, retrospectively, follow-up data was collected until 30 April 2023. The Kaplan–Meier method was used to evaluate transplant-free survival time in the study population over 6 months and the long-term follow up, with a log-rank test used to analyze differences between groups (IPF versus non-IPF ILD). Further, a cox proportional hazard regression analysis was performed and included retrospective follow-up until 30 April 2023. The cox proportional hazard regression analysis was applied to identify associations of VAScough and SPD with transplant-free survival time including the covariates baseline FVC and IPF. In the Cox proportional hazard regression analysis SPD were analyzed per 1000 SPD. p values < 0.05 were considered statistically significant. Data were statistically analyzed by SPSS version 25.0 and 29.0  or GraphPad Prism version 8.0 for Mac , with p < 0.05 considered statistically significant.Continuous variables are presented as the mean ± standard deviation (SD), with categorical variables summarized by frequency and percentage. The Mann-Whitney test was used to compare continuous variables, the Chi square and Fisher’s exact tests were used to compare categorical variables, and Pearson’s correlation test identified correlations between parameters. To calculate VASn = 13; non-IPF n = 22) were included in the analyses as depicted in n = 7), chronic hypersensitivity pneumonitis (n = 7), unclassifiable ILD (n = 5) and NSIP (n = 3). From July 2017 until August 2018, 40 patients consented to participate in the study. Since five patients had fewer than 4 days of activity measurements, only 35 patients (IPF n = 11) patients with IPF were receiving antifibrotic therapy. Among patients with non-IPF ILD 72.7% (n = 16) were receiving immunosuppressive therapy and 22.7% (n = 5) were receiving antifibrotic therapy. There were no differences between the IPF and non-IPF ILD groups in terms of comorbidities  were able to perform a DLCO measurement. Patients’ characteristics are summarized in bidities . The meap = 0.023). Comparing patients with IPF and those with non-IPF ILD, patients with IPF had significantly more limitations in terms of KBILD values compared to those with non-IPF ILD . Over time, neither KBILD nor SGRQ changed significantly in non-IPF ILD or IPF.At baseline, mean KBILD was 52.4 ± 11.3 and mean SGRQ was 49.2 ± 18.7, with the measures correlating moderately with each other , and moderately with the active time  and calorie expenditure . Additionally, active time, calorie expenditure, and the distance covered correlated with each other .The mean ± SD wearing time of the wristband accelerometer was 14.7 ± 2.4 h per day. Our cohort had a mean of 5008 ± 4234 SPD at baseline , with distance covered 2874 ± 2564 m, active time  4.8 ± 2.4 h/day, and calorie expenditure of 2167 ± 521 kcal calculated by the device. SPD correlated strongly with the distance covered , SPD , calorie expenditure (p = 0.827) or active time  with mean ± SD cough burden as measured with the VAScough of 3.3 ± 2.6 (range 0 to 8.8). There was no difference in VAScough between patients with and without gastroesophageal reflux disease (p = 0.12). For KBILD, but not SGRQ, there was a significant inverse correlation with VAScough , although change in VAScough over 6 months was not associated with VAScough at baseline .Patients with IPF had a mean ± SD VAScough was 2.5 ± 2.4 at baseline. A mean ± SD of 20.8 ± 8.8 VAScough measurements were obtained over 6 months, with an overall decrease in mean VAScough , and the change of VAScough over 6 months was independent from VAScough at baseline .In non-IPF ILD, the mean ± SD VAScough in IPF and non-IPF ILD, we identified marked differences between the two groups. Baseline VAScough was significantly higher in IPF than in non-IPF ILD (p = 0.020). While no association between SPD or active time and cough could be found in any group, in non-IPF ILD but not in IPF VAScough showed a significant association to FVC, DLCO and the 6MWD . Further, the variation of VAScough was significantly lower in patients with IPF than in those with non-IPF ILD (p = 0.012).When comparing the findings on VASthe 6MWD . In addin = 1; non-IPF ILD n = 1) and three patients underwent lung transplantation . While there were no significant differences in age (p = 0.91), FVC (p = 0.24), DLCO (p = 0.88) or active time (p = 0.09) between patients who died or underwent lung transplantation vs. the remaining 30 patients, mean SPD was significantly lower  and significantly lower SGRQ . Transplant-free survival did not differ between patients with IPF and non-IPF ILD within the first 6 months .Over six months, two patients died due to respiratory failure , 28.6% of the patients underwent lung transplantation  and 17.1% of the patients were lost to follow-up . The mean ± SD transplant-free survival time was 1342 ± 145 days . In the regression analysis VAScough and SPD  were independent predictors for transplant-free survival  HR: 0.606; 95%-CI; p = 0.011) including the covariates baseline FVC and IPF . This could be due to a greater overall burden of cough in IPF, which is already present in less advanced disease. Our data support the need to develop strategies to better alleviate cough (including new therapeutic agents), and to incorporate cough management in ILD care strategies [cough is a standardized, easy-to-collect instrument that could quickly be integrated into clinical routine.While it has been shown that cough is a significant, distressing symptom in IPF , clinicaval time . In our rategies . Given tcough. The correlation with cough seems to be robust as it was not only seen at baseline but also at the 3 months visit. Although KBILD and SGRQ correlated moderately at baseline, the relationships between KBILD and cough and activity were not observed for SGRQ. This contrasts with another study, which identified an association between SPD and SGRQ [To evaluate the impact of cough and activity on HRQoL, we used the two questionnaires KBILD and SGRQ. Overall, mean baseline KBILD was similar to a previously published study in patients with ILD at an outpatient clinic . KBILD cand SGRQ . The reaand SGRQ , are betn = 6; non-IPF ILD n = 6) the subjective progression of ILD was accompained by a FVC decline of >5% absolute over the last year, retrospectively indicating a pogressive phenotype according to the current guideline [cough at baseline showed significant differences compared to the other patients. The limited number of patients, the lung transplants and the advanced stage of the diseases could explain why the transplant-free survival of patients with IPF was not significantly different from that of patients with non-IPF ILD.We acknowledge the inherent limitations of our study. First, this was a single-center study with a limited number of patients. Further, our patients were already in an advanced stage of disease, which could be one reason for the very high prevalence of cough. Moreover, our accelerometer was not an existing research instrument: To measure physical activity, we used an ordinary fitness tracker. Our device was one of the five most often used fitness tracker (wrist-worn) brands in research projects . We are uideline . Interescough correlating with DLCO, and patients who subsequently died or underwent lung transplantation having higher cough burden. In particular, patients with IPF reported more cough, which increased over time. While we did not observe an association between cough and physical activity, SPD significantly correlated with lung function and exercise capacity and was significantly reduced in patients who subsequently died or underwent lung transplantation. Moreover, VAScough and SPD were independent predictors for transplant-free survival in the study cohort. Both cough and physical activity should be key components in disease management.In conclusion, while physical activity does not differ between IPF and non-IPF ILD, there were marked differences in cough between the two groups. Cough was present in over 90% of all patients with advanced ILD, with the VAS


In this retrospective study, we aimed to develop a nomogram to predict recurrence during a 1-year period of spinal manipulation/mobilization (SM/M) in patients with low back pain (LBP) with greater pain intensity, more severe comorbid conditions, or a neuropathic component.A total of 786 consecutive patients with LBP treated with SM/M as primary therapy were divided into training (n = 545) and validation (n = 241) sets. Cox regression analyses were used to assess the relative value of clinical factors and lumbar magnetic resonance imaging features associated with recurrence during the 1-year period. Predictors of recurrence with significant differences were used to construct a nomogram in the training set. We evaluated the performance of the model on the training and validation sets to determine its discriminative ability, calibration, and clinical utility. The prognostic value of the nomogram for predicting recurrence was assessed using Kaplan–Meier analysis and time-dependent receiver operating characteristic analyses.A nomogram comprising hospitalization time, previous history of LBP, disease duration, lumbar range of motion, lower extremity tendon reflex, muscle strength, ratio of herniation to uncompressed dural sac area, and Pfirrmann classification was established for recurrence during a 1-year period after SM/M in patients with LBP. Favorable calibration and discrimination were observed in the nomogram training and validation sets . Decision curve analysis confirmed the clinical utility of the nomogram. Over a 1-year period, the nomogram showed satisfactory performance in predicting recurrence in LBP after SM/M.We established and validated a novel nomogram that can accurately predict a patient's risk of LBP recurrence following SM/M. This realistic prognostic model may aid doctors and therapists in their decision-making process and strategy optimization for non-surgical treatment of LBP using SM/M.The online version contains supplementary material available at 10.1186/s12998-023-00500-5. Low back pain (LBP) is a prevalent cause of disability worldwide . At the Recently, with greater concordance among international guidelines on LBP, non-invasive treatment has become the dominant option, including passive treatment, drug-based therapy, physiotherapy, and exercise . HoweverSM/M works by improving the mobility of the spine and hips to reduce pain and dysfunction, and the core operations include both mobilization and manipulation . MobilizHence, in this study, we aimed to develop and validate a novel multidimensional nomogram which could predict 1-year recurrence of LBP after SM/M.The following article was prepared in accordance with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) reporting checklist , and the requirement for informed consent was waived because of the retrospective nature of this study. We screened the clinical records of consecutive inpatients with LBP with or without radicular pain who were treated at the Hangzhou TCM Hospital, affiliated with the Zhejiang Chinese Medical University, from November 2014 to October 2021. Patients who were recommended non-surgical treatment since their neurological examination did not reveal sphincter incontinence or foot drop during were identified.Patients were included if they met the following criteria: (1) aged between 18 and 70 years; 2) no restrictions on sex or occupation; (3) LBP with or without radicular pain , and con no restrDemographic data including age, sex, occupation, body mass index (BMI), occupation and chronic health problems such as diabetes, hypertension, and cardiopathy were reviewed using medical records. Additionally, information was collected on overall pain scores using the numerical rating scale (NRS), radicular pain in the lower extremities, tendon reflexes and muscle strength, lumbar range of motion, straight leg raise test on admission, and whether a combined epidural was used.All patients were scanned with a 1.5 T MRI scanner , and sections were obtained at a thickness of 4 mm in both the axial and sagittal planes. Routine intervertebral disc protocols consisted of sagittal T1-weighted (T1WI) and T2-weighted (T2WI) images. T2WI images were obtained by axial MRI scanning with the vertebral body aligned parallel to the inferior endplate. The following qualitative imaging parameters were independently assessed by both a clinician and a radiologist : (1) chahttps://www.r-project.org/). All eligible samples were randomly separated into the training and validation (7:3) groups using the R caret package. For continuous data with a normal or an abnormal distribution, the Student’s t- and Wilcoxon Mann–Whitney U test were used to analyze the statistical significance of differences between the with and without recurrence groups. Categorical variables were compared using the chi-squared or Fisher’s exact test. The reported statistical significance levels were two-sided, and statistical significance was set at P-values less than 0.05.All statistical analyses were performed using SPSS for Windows  and R software , and those that were non-significant but clinically important, were entered into the multivariable analyses via the Cox regression model. Based on the results of the multivariable analysis, a nomogram was formulated using the survival and rms packages of R software. Backward stepwise selection was performed using the likelihood ratio test with Akaike’s information criterion as the stopping rule [In the training set, univariate analyses based on clinical characteristics and imaging features were performed using SPSS software. Variables that achieved significance  . The perTo evaluate the clinical utility of the nomogram, decision curve analysis (DCA) was performed to calculate the net benefits at different threshold probabilities in the full dataset, combining the training and validation sets . We sougIn total, 786 consecutive patients with LBP who met the inclusion criteria and were treated in our hospital between November 2014 and October 2021 were included. MRI confirmed varying degrees of disc degeneration or herniation, with or without radicular pain. Subsequently, 545 and 241 patients were assigned to the training and validation sets, respectively  12.38 years), with 45.93% males and 54.07% females. The highest number of herniated disc segments was observed in lumbar (L) 5-sacral (S) 1 (49.36%), followed by L4–L5 (44.78%), and other (5.85%). The Pfirrmann classification of disc degeneration found that grades III (31.81%) and VI (32.95%) were the most common, followed by grades II (12.09%), V (17.43%), with VI (4.20%) and VII (1.52%) being the least common. There was no important difference in clinical characteristics and imaging features between the two sets, supporting their use as training and validation sets , previous history of LBP (P < 0.001), disease duration (P < 0.001), lumbar range of motion (P = 0.027), lower extremity radicular pain (P < 0.001), lower extremity tendon reflex and muscle strength (P < 0.001), and information collected on MRI—such as nerve root impingement (P < 0.001), ratio of intraspinal herniation area (P = 0.003), ratio of herniation to uncompressed dural sac area (P = 0.018), and Pfirrmann classification (P < 0.001)—were associated with the recurrence of LBP after SM/M at 1-year follow-up  such as age, sex, BMI, occupation, straight leg raise test, apical location of herniation, and characteristics of the disc herniation were analyzed with the indicators described above in a multivariable analysis because they were considered to have valuable clinical significance. Finally, hospitalization time (P = 0.016), previous history of LBP (P = 0.016), disease duration (P = 0.040), lumbar range of motion (P = 0.029), lower extremity tendon reflex (P < 0.001), muscle strength (P = 0.005), ratio of herniation to uncompressed dural sac area (P < 0.001), and Pfirrmann classification (P < 0.001) were identified as predictors of recurrence  in the training and 0.779 (95% CI 0.725–0.833) in the validation Fig. A set. WeP < 0.0001)  Fig. A had a s01) Fig. B.Fig. 6TWe established and validated a novel nomogram based on a combination of clinical characteristics and lumbar MRI features to predict the risk of recurrence within 1 year in patients with LBP who have been treated with SM/M. The primary retrospective cohort in this study was obtained from 7 years of inpatient data from the massage department of our hospital. This department represents standard technology or medical services in the field of SM/M in Hangzhou City. Through univariate analysis and subsequent multivariable analysis, we identified hospitalization time, previous history of LBP, disease duration, lumbar range of motion, lower extremity tendon reflex and muscle strength, ratio of herniation to uncompressed dural sac area, and Pfirrmann classification as independent prognostic factors for LBP recurrence after SM/M.These findings were highly concordant with those of previous reports on risk factors for LBP. A previous history of LBP , diseaseA meta-analysis of 47 randomized controlled trials (RCTs)  and anotUnlike other clinical trials investigating SM/M for LBP, our inclusion criteria , 40 alloThe mechanism of SM/M remains to be determined, but it is likely to be complex and controversial. For the potentially malignant factors mentioned above, the rationale for manipulation is recognized to be the correction of disc displacement, release of adhesive fibrosis surrounding prolapsed discs or facet joints, entrapped synovial folds or plicae, relaxation of hypertonic muscles, and unbuckling displaced motion segments , 45. SM/Therefore, we sought to develop a nomogram to predict recurrence-free conditions in non-surgical LBP patients after SM/M and identify participants who would respond better to SM/M. Our prognostic model indicated that patients with LBP with a first episode, short-term disease course, no limitation of movement or lumbar radiculopathy, minor disc herniation, or mild degeneration would be better treated with SM/M. It revealed good calibration and discriminative power after internal validation; however, external validation is recommended before implementation in clinical practice. Unlike previous studies investigating the recurrence of LBP after SM/M, our most significant improvement was the validation of predictors . Knecht This study has some limitations. First, it is retrospective and included participants from a single institution. Thus, prospective cohort-based analyses and external validation of additional sites are required. Second, we did not draw precise etiological subgroup distinctions for LBP, nor is there a good distinction between acute and chronic LBP. This is another reason prospective investigations are required to further confirm the reliability of our nomogram. To better understand the effectiveness of SM/M, a more detailed prognostication among different LBP types needs to be performed. Finally, research incorporating radiomics into predictive nomograms should be conducted in the future, as both qualitative and quantitative imaging features suffer from certain constraints.A nomogram incorporating clinical factors and imaging features achieved satisfactory performance in individualized prediction of the 1-year recurrence-free period of LBP after SM/M, allowing optimization of the non-surgical treatment strategy in patients. Further validation is required in future prospective studies and with data from external cohorts.Additional file 1: TRIPOD Checklist: Prediction Model Development and Validation.Additional file 2: Spinal manipulation/mobilization.Additional file 3: Data acquisition method of imaging features.Additional file 4: Comparisons of clinical characteristics and imaging features of patients in the training and validation set.Additional file 5: Univariate and multivariate analysis of recurrence based on population information, clinical risk factors and imaging features in the training set.


Pelteobagrus fulvidraco), sodium selenite (Na2SeO3), Se yeast, and selenium-enriched Spirulina platensis (Se–SP) were supplemented in the control diet at 0.30 mg Se/kg feed to formulate four diets. The experimental period lasted 50 days. The results showed that Se levels in the plasma, liver, muscle, and whole body were significantly increased by dietary Se yeast supplementation (P < 0.05) but showed no change in response to Na2SeO3 (P > 0.05). The three types of Se all increased the firmness and decreased the fracturability of the muscles (P < 0.05), but only Na2SeO3 resulted in higher springiness, flexibility, stringiness, and stickiness (P < 0.05). In addition, the muscle n−3 polyunsaturated fatty acid (PUFA) content was increased by Se yeast (P < 0.05). Regarding antioxidant capacity, dietary Se yeast and Se–SP supplementation improved hepatic glutathione peroxidase activity but decreased hepatic malondialdehyde content (P < 0.05). Given these results, Se yeast was found to be the optimal source of Se for yellow catfish for higher tissue retention, antioxidant capacity, and PUFA levels. Dietary Se is an effective way to regulate the meat quality and antioxidant capacity of yellow catfish.To assess the effect of dietary selenium (Se) sources on the meat quality and antioxidant capacity of yellow catfish ( Epinephelus malabaricus) 3] found  catfish . Therefo2SeO3 on the amino acid profiles and the increase in n−3 PUFA levels in yellow catfish muscle by dietary Se yeast supplementation. For juvenile grouper, both dietary organic and inorganic Se supplementation enhanced meat quality [2SeO3 supplementation may be related to higher whole-body lipid levels.Several kinds of minor elements, including Se, as feed additives, could improve meat quality , 12, 41.S. platensis [GPX activity is a useful index for assessing the bioavailability of Se . Our reslatensis .2SeO3 supplementation was found to upregulate the expression of gpx4 and selenow, which was inconsistent with the total Se accumulation and GPX activity in the liver. We only determined the hepatic expression of three selenoprotein genes. In addition, the results were in agreement with the findings of other studies indicating that changes in protein expression did not always correspond to changes in mRNA [Different selenoproteins have different functions and thus show different transcriptional responses, and selenoproteins exhibit different patterns in different tissues , 39. In  in mRNA .n−3 PUFA levels. Dietary supplementation with Se yeast is an efficient way to produce Se-enriched fish meat, which is a good source of Se for human health. Dietary Se is an effective way to regulate the meat quality and antioxidant capacity of yellow catfish.In conclusion, Se yeast seems to be the optimal Se source for yellow catfish for higher tissue retention, antioxidant capacity, and


Intracranial atherosclerotic disease (ICAD) poses a significant risk of subsequent stroke but current prevention strategies are limited. Mechanistic simulations of brain hemodynamics offer an alternative precision medicine approach by utilising individual patient characteristics. For clinical use, however, current simulation frameworks have insufficient validation. In this study, we performed the first quantitative validation of a simulation-based precision medicine framework to assess cerebral hemodynamics in patients with ICAD against clinical standard perfusion imaging. In a retrospective analysis, we used a 0-dimensional simulation model to detect brain areas that are hemodynamically vulnerable to subsequent stroke. The main outcome measures were sensitivity, specificity, and area under the receiver operating characteristics curve (ROC AUC) of the simulation to identify brain areas vulnerable to subsequent stroke as defined by quantitative measurements of relative mean transit time (relMTT) from dynamic susceptibility contrast MRI (DSC-MRI). In 68 subjects with unilateral stenosis >70% of the internal carotid artery (ICA) or middle cerebral artery (MCA), the sensitivity and specificity of the simulation were 0.65 and 0.67, respectively. The ROC AUC was 0.68. The low-to-moderate accuracy of the simulation may be attributed to assumptions of Newtonian blood flow, rigid vessel walls, and the use of time-of-flight MRI for geometric representation of subject vasculature. Future simulation approaches should focus on integrating additional patient data, increasing accessibility of precision medicine tools to clinicians, addressing disease burden disparities amongst different populations, and quantifying patient benefit. Our results underscore the need for further improvement of mechanistic simulations of brain hemodynamics to foster the translation of the technology to clinical practice. DespiteThough ICAD is a chronic condition where regular monitoring of disease progression would provide important insights, intracranial disease progression is not typically assessed for numerous reasons. On the one hand, current hemodynamic tests that cover all brain areas are unfit for repeated measurements and come with a list of disadvantages. Bolus-tracking methods such as CT perfusion or dynamic susceptibility contrast (DSC) MRI are hard to standardise, require expert level post-processing, and the administration of potentially harmful contrast agents , 8. ArtePrecision medicine is an approach where treatments are targeted on the individual characteristics of patients, using genotypic, phenotypic, psychosocial factors or biomarkers . SeminalThus, the aim of this study is to assess the ability of the proposed simulation framework to identify patients with ICAD that are at high risk of subsequent stroke because of their individual cerebral hemodynamics. For this, we measured the accuracy of the simulation in terms of sensitivity, specificity and area under the ROC curve (AUC) to predict areas of hemodynamic vulnerability that were defined by quantitative perfusion imaging with the clinical reference standard DSC-MRI.2.2.1.We conducted an observational retrospective study to determine the diagnostic accuracy of a previously published simulation framework . For thi2.2.We included patients with ICAD of the PEGASUS trial conducted at Charité-Universitätsmedizin Berlin. Patients have been recruited at the Charité Department of Neurology and affiliated out-patient services between August 2011 and March 2015. Prior to the study all patients gave written informed consent. The study was approved by the authorised institutional review board of Charité-Universitätsmedizin Berlin and was conducted according to the principles expressed in the Declaration of Helsinki. The patient collective has been described before . Inclusi2.3.MR-imaging was performed on a 3 T whole-body system  using a 12-channel receive RF coil  tailored for head imaging. Subjects who did not undergo all imaging sequences of the protocol had to be excluded from the analysis.2.3.1.3; matrix size: 312 × 384 × 127; TR/TE = 22/3.86 ms; flip angle = 18°; time of acquisition = 3 min 50 s.The parameters for Time-of-flight (TOF) imaging were: voxel size = 0.5 × 0.5 × 0.7 mm2.3.2.3; slices = 21; acceleration factor = 2; TR/TE = 1,390 /29 ms; flip angle = 60°; time of acquisition = 1:54 min; 5 mL Gadovist  followed by a 25 mL saline flush, injected using a power injector  at a rate of 5 mL/s. Acquisition parameters are in line with the recommendations by the Acute Stroke Research Imaging Roadmap (The Dynamic susceptibility contrast MRI (DSC-MRI) protocol consisted of a series of 80 whole-brain images using a single-shot free induction decay (FID)-EPI sequence. DSC parameters were in detail: field of view = 224 × 224 mm; voxel size = 1.8 × 1.8 × 5 mm Roadmap .2.3.3.3; TR/TE = 1,900/2.25 milliseconds; time of acquisition = 4:26 min.As an anatomic reference, a 3D, T1-weighted, magnetization prepared rapid gradient-echo (MPRAGE) sequence with the following parameters was used: voxel size = 1.0 × 1.0 × 1.0 mm2.4.in silico following the approach previously published by our group  of 70 mmHg was assumed to be the lower limit up to which healthy subjects are able to compensate for hemodynamic impairment keeping regional cerebral perfusion stable , 31. Thi map see .2.6.p < 0.001). Hence, a relMTT threshold of 1.387 as measured with DSC-MRI was adopted to denote vulnerability on the reference test of this study. This means that when a patient’s MTT in the MCA area of the side of stenosis was increased by a factor larger than 1.387 compared to the MTT in the respective contralateral MCA area, the reference test was counted as positive . For this, maps of MTT were created from raw DSC images by parametric deconvolution of a regional concentration time curve with an arterial input function (AIF) , a perfusion parameter, have been shown to be a reliable indicator of hemodynamic impairment in patients with ICAD . Based oon (AIF)  using PGon (AIF) , 38. MTTFurther image processing steps were performed in a Nipype workflow RRID: SCR_002502): On MPRAGE and DSC images we performed (1) intensity non-uniformity correction , (2) skull-stripping , and (3) co-registration. Only cortical grey matter and basal ganglia regions were included in this analysis to account for perfusion differences between grey matter and white matter. (4) Grey matter masks were created on MPRAGE using the FAST tool , or a difference in TOF-MRI protocol (4 cases). Vulnerability to stroke status was successfully simulated for all 68 subjects following the precision medicine framework of our group . DSC-MRIOf all subjects 39.7% identified as female, median age was 57 years (range 29–82 years). Two thirds of the subjects suffered from stroke prior to the study, irrespective of aetiology; 17.6% had a prior transient ischemic attack (TIA). Summary statistics for demographic and clinical characteristics are shown in 3.2.DSC parameter map quality of 68 cases was visually assessed by two independent raters; consensus rating was reached in all cases. 97% of DSC MTT maps were rated either very good (25%), good (44%), or sufficient (28%) and thus included for analysis. However, 22 of the 68 cases (32%) showed motion artefacts on visual analysis, diminishing reference standard quality. In six of the 68 cases (9%) the motion artefact exhibited a clear left-to-right heterogeneity, skewing side-wise measures of relMTT. In 2 of 68 cases (3%) DSC quality was rated uninterpretable due to low signal-to-noise ratio, resulting in no reference standard for these subjects.3.3.On DSC-MRI 17 of 66 cases exhibited vulnerability to stroke with elevated relMTT above 1.387. In the simulation we detected 11 of these 17 cases of vulnerability, representing a true positive rate (TPR) of 64.7% and false negative rate (FNR) of 35.3%. 49 cases exhibited relMTT of less than 1.387 on DSC-MRI and were thus not vulnerable to stroke. 33 of these 49 cases were correctly identified by the simulation as not vulnerable, corresponding to a true negative rate (TNR) of 67.4% and a false positive rate (FPR) of 32.7% see .Based on these results, the sensitivity of the simulation to detect patients vulnerable to stroke in MCA-territory as denoted by DSC perfusion-MRI was 0.647, 95% CI . The specificity was 0.674, 95% CI . The overall accuracy of the simulation was 0.667. The geometric mean of sensitivity and specificity was 0.66 with an F1-score of 0.5. A ROC curve for varying thresholds of 3.4.Of the 17 patients with vulnerability to stroke on DSC-MRI, 10 showed full occlusion of the examined vessel (59%), 13 suffered from prior stroke (77%), one from prior TIA (6%). Of the 51 patients without vulnerability to stroke on DSC-MRI, 26 showed full occlusion (51%), 33 suffered from prior stroke (65%), 11 from prior TIA (22%). No information on alternative diagnoses of participants was available.3.5.Imaging for both simulation  and reference test  has been acquired in one session. No clinical interventions other than the ones needed for imaging, i.e., administration of contrast agent, have been performed in between index test and reference standard.4.We performed the first quantitative validation of a framework for the personalised simulation of cerebral hemodynamics in patients with ICAD against a clinical perfusion imaging standard. The presented results indicate a low-to-moderate performance of the simulation framework to predict hemodynamic vulnerabilities. Whilst simulation approaches for hemodynamic assessment of patients with chronic cerebrovascular disease remain promising, our results indicate that further research is required to improve their performance.in situ thrombotic occlusion, artery-to-artery embolism, hemodynamic insufficiency or branch occlusion  models, were shown to be a powerful tool for numerical representation of complex flow patterns in single cerebral arteries or lesions in ICAD , 46–48, Based on such theoretical considerations, lumped models may mark a significant leap towards a personalised medicine approach in care for patients with cerebrovascular diseases. Our empirical results, however, indicate that the innovative simulation approach under investigation is still exploratory and needs further refinement to change clinical practice. Based on the data presented, the accuracy for personalised simulation of cerebral hemodynamics did not reach the clinical reference standard DSC-MRI. A low-to-moderate sensitivity and specificity imply that the framework is not yet able to detect patients at high risk of subsequent stroke reliably. This may be attributed to the fact that mechanistic simulations of highly complex systems make assumptions for reasons of computational feasibility. Firstly, blood flow is assumed to be Newtonian. However, the rheological properties of blood, a non-Newtonian fluid, have been shown to influence local hemodynamics at vessel bifurcations and narrowings . This ha outflow . As a bo15O-water PET or intraoperative flow measurements. Whilst these are expensive and data scarce, artefact-ridden clinical reference standards such as DSC-MRI may pose insufficient as a benchmark for widespread clinical use. Lastly, for patients this currently means that the diagnosis of ICAD continues to rely on potentially harmful perfusion imaging, duplex sonography, and digital subtraction angiography. Thus, there remains an unmet need for safe diagnosis and tracking of disease progression in ICAD.What could now be the way forward for simulation methods in ICAD? There are various research opportunities on how to close the gap to clinical practice. Firstly, to increase diagnostic power researchers may consider incorporating additional patient information into their applications. Future work could explore the use of readily available multi-modal data sources, both clinical, imaging, and administrative. Instead of using transcranial Doppler sonography (TCD) only for determining GoS, as was done in the PEGASUS study, the use of flow measures from TCD as personalised boundary conditions could improve accuracy of our group’s simulation. Shen et al. successfully implemented personalised boundary conditions from TCD flow data for simulating cerebral blood flow . Secondl15O-water PET  and the German Federal Ministry of Education and Research through a Go-Bio grant (PREDICTioN2020 grant no. 031B0154 lead: DF).VM, TK, and AH reported receiving personal fees from ai4medicine outside the submitted work. Whilst not related to this work, JS reports receipt of speakers’ honoraria from Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Gore, Maquet, Paion, Sanofi, Takeda pharma, UCB, and Berlin Chemie. DF reported receiving grants from the European Commission, reported receiving personal fees from and holding an equity interest in ai4medicine outside the submitted work.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The existing diagnostic methods of epilepsy such as history collection and electroencephalogram have great limitations in practice, so more reliable and less difficult diagnostic methods are needed.By characterizing oral microbiota in patients diagnosed with epilepsy (EPs) and patients whose seizures were under control (EPRs), we sought to discover biomarkers for different disease states. 16S rRNA gene sequencing was performed on 480 tongue swabs .Streptococcus, Granulicatella, and Kluyvera, while the abundance of 14 genera, including Peptostreptococcus, Neisseria, and Schaalia, is significantly reduced. The area under the receiver operating characteristic curve (AUC) of oral microbial markers in the training cohort and validation cohort was 98.85% and 97.23%, respectively. Importantly, the AUC of the biomarker set achieved 92.44% of additional independent validation sets. In addition, EPRs also have their own unique oral community.Compared with normal individuals, patients with epilepsy exhibit increased alpha diversity in their oral microbiota, and the oral microbial communities of the two groups demonstrate significant beta diversity differences. EPs exhibit a significant increase in the abundance of 26 genera, including This study describes the characterization of the oral microbiome in EP and EPR and demonstrates the potential of the specific microbiome as a non-invasive diagnostic tool for epilepsy. There iGut microbes and the brain communicate with each other via vagus nerve activation, endocrine and immune response regulation, and microbial metabolite production . NeuroloThe oral microbiome is a microbiome library that continuously supplements the gut microbiome, and at least one-third of oral microbiome cells enter the intestinal tract of healthy people through the digestive tract . A 16S rBased on the results of previous intestinal microbiota, we attempted to further reveal changes in the oral microbiota in epilepsy patients using a large cohort and identify related biomarkers. We hope that the exploration of oral microbiota will provide new ideas for the diagnosis and treatment of epilepsy.22.1This study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (No. 2021-KY-0574-002). All samples and clinical data involved in this study were collected with the informed consent from each participant. From early 2019 to late 2020, 161 tongue swab samples were collected from 161 hospitalized patients diagnosed with epilepsy (EPs). In total, 161 EPs were all newly diagnosed with epilepsy by a neurologist. Out of the 161 patients with epilepsy, a subset of 22 was followed up for 3–4 months, and during this follow-up, we observed that these 22 patients achieved seizure control through drug treatment. At the conclusion of the follow-up period, tongue swabs were collected from these 22 patients whose seizures were under control (EPRs). In the second half of 2021, we collected corresponding tongue swabs from 29 patients with newly diagnosed epilepsy recruited from the same urban district as an independent test cohort. EP and EPR were selected by neurology professionals concerning our inclusion and exclusion criteria. The healthy controls (HCs) consisted of 527 volunteers who underwent a physical examination at the First Affiliated Hospital of Zhengzhou University from 2019 to 2020. The inclusion and exclusion criteria of subjects are presented in 2.2As described by 2.3® 9700 PCR thermocycler  is as follows: initial denaturation was performed at 95°C for 3 min; the process involved denaturation at 95°C for 30 s, annealing at 55°C for 30 s, and extension at 72°C for 45 s, which were repeated for 27 cycles; followed by a single extension at 72°C for 10 min. Finally, the reaction was kept at 4°C. The reaction system consisted of template DNA (10 ng), TransStart FastPfu DNA Polymerase (0.4 μL), 5 μM forward primer (0.8 μL), 5 μM reverse primer (0.8 μL), 5 × TransStart FastPfu buffer (4 μL), 2.5 mM dNTPs (2 μL), and ddH2O (up to 20 μL). PCR products were detected using 2% W/V agarose gel, and bands were extracted and purified by AxyPrep DNA Gel  and the PCR Clean-Up System.As usual, we extracted DNA from the microbes using the Qiagen Mini Kit  following the manufacturer’s instructions . The DNA2.4The DNA library was built according to the manufacturer’s instructions. The gene sequences were sequenced on an Illumina MiSeq platform of Shanghai Mobio Biomedical Technology Co., Ltd., China. The amplicon reading was processed by following these steps: (a) the double-ended sequencing readings for each library are overlapped using FLASH version 1.2.10, with default parameters ; (b) The2.5An equal number of reads were randomly selected from each sample, and then OTUs were binned through the UPARSE pipeline. We ensure that OTUs include all samples collected at different times. The similarity threshold is set to 97%. Finally, according to the developer’s documentation, we use the RDP classifier V.2.6 to annotate the sequences.2.6The alpha diversity and beta diversity of microorganisms were obtained based on the OTU analysis of samples. The alpha diversity including the Ace index, Chao index, Shannon index, Simpson index and observed OTUs were calculated by the R program package “vegan.” Non-metric multidimensional scaling (NMDS), principal component analysis (PCA), and principal coordinate analysis (PCoA) were analyzed by R packetp < 0.05) to find statistically significant variables and then evaluates the magnitude of the impact of each variable on the differential effect between the two groups by LDA [LDA score (log10) >3]. For p-values, multiple testing was performed using the false discovery rate.The Wilcoxon rank-sum test was used to compare the two groups of bacteria in different phylum and genus categories. Linear discriminant analysis (LDA) effect size (LEfSe)2.7The KEGG orthology (KO) and KEGG pathway/module maps were built using PICRUSt22.8p < 0.05), to obtain OTU with inter-group differences. Based on the difference in the OTU abundance profile of the discovery queue, 5-fold cross-validation is carried out on the random forest model, where all parameters are default values, except for importance = TRUE. The determined set of optimal OTUs is used to calculate the probability of the disease index of the discovery queue and the validation queue. The R package  was used to construct the receiver operating characteristic (ROC) curve to evaluate the diagnostic capability of the constructed model, where the area under the receiver operating characteristic curve (AUC) represents the ROC effect  and HCs (n = 200) were compared. For the two groups of continuous variables with independent design, the two-sample t-test was applied for comparison between the groups assuming normal distribution and homogeneity of variance, and the approximate t-test was used for comparison between the groups assuming normal distribution and non-homogeneity of variance. The statistical analysis was performed using SPSS V.26 for Windows . Statistical significance was defined by p < 0.05 (two-tailed), without post-analysis and alpha adjustment.For the basic information of the participants, the following statistical analysis methods were used. The continuous and categorical variables were expressed as mean (standard deviation) and percentage, respectively. Tongue swab samples from EPs , 22 patients whose seizures were under control (EPRs), and 301 healthy controls (HCs)] from Henan Province were included in this study for statistical analysis. We randomly selected tongue swab samples at the ratio of 2:1 as the discovery cohort and verification cohort. The specific research framework is shown in 3.2p < 0.05). EP exhibited statistically significant differences in red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, albumin, uric acid (UA), estimated glomerular filtration rate (eGFR), and total bilirubin (TBIL) compared with HC (p > 0.05), but these values were all within the normal range.The basic information of 100 EPs and 200 HCs for oral samples is shown in 3.3In the oral microecological discovery cohort (100 EPs and 200 HCs), the species accumulation curve and Shannon–Wiener curve showed that the sample size and sequencing data were sufficient for both groups ,B. RegarFirmicutes, Spirochetes, and another two phyla increased, while the relative abundance of Actinobacteria decreased. At the genus level   (A heatmap  was draw LDA >3) . AdditioLDA > 3)  most relLDA > 3) .3.4p < 0.0001) (p < 0.0001) (p < 0.0001)  . Further 0.0001) , and the 0.0001) . To furt 0.0001) , and the 0.0001) . These r3.5We followed previously enrolled EP and eventually collected tongue swabs from 22 EPRs. Under the premise of sufficient sample size and sequencing data for both groups , alpha dThe mean species composition distribution and bacteria with statistical significance at the genus (phylum) level between the two groups are shown in p < 0.05, LDA >3) (A heatmap  indicate LDA >3) . Compare LDA >3) .p < 0.0001)  . Hence, 3.6Schaalia in EP decreased , OTU21 (Leptotrichia)] in EPR was lower than that of EP, but the relative abundance of OTU35  and OTU224  was higher.Among the differential OTUs screened by the Wilcoxon rank-sum test , the rel4In this study, we compared the oral microflora of a large sample of patients with epilepsy to that of healthy subjects and identified differences in the oral microflora of the two groups. This study showed that the oral microbiome diversity of patients with epilepsy was higher than that of healthy controls, but there was no statistically significant difference in oral microbiome diversity before and after seizure control, even though the values were reduced. In the study by Streptococcus and Leptotrichia in EP increased, while the relative abundance of Neisseria, Haemophilus, Rothia, and Schaalia decreased. However, the relative abundance of Streptococcus in EPR still increased after seizure control compared with HC. In a retrospective analysis of 145 children with central nervous system infections, the cerebrospinal fluid culture of 26.1% of infected patients showed the presence of Group B Streptococcus and Streptococcus pneumoniae . The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.XL: Data curation, Formal analysis, Writing – review & editing. ZL: Data curation, Writing – original draft. TW: Resources, Software, Writing – review & editing. JL: Data curation, Resources, Writing – review & editing. YC: Methodology, Resources, Writing – review & editing. SsL: Resources, Writing – review & editing. LJ: Investigation, Resources, Writing – review & editing. ShL: Resources, Writing – review & editing. YL: Investigation, Methodology, Resources, Writing – review & editing. YJ: Investigation, Methodology, Resources, Writing – review & editing. ZR: Data curation, Funding acquisition, Writing – review & editing.


To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR).P < 5 × 10–8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10–5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls.We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(Clostridia , Adlercreutzia  and Victivallis  were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira  was negatively with the risk of UIA and Sutterella  was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella  was negatively with the risk of UIA and Rhodospirillaceae  was positively related with the risk of UIA. The results suggest that Streptococcus  and Peptostreptococcaceae  may increase the risk of UIA according to genome-wide statistical significance thresholds.On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.The online version contains supplementary material available at 10.1186/s12883-023-03288-2. Intracranial aneurysm (IA) is confined, pathological dilatations of the walls of intracranial arteries that are at risk of rupture. About 85% of spontaneous subarachnoid hemorrhage(SAH) is due to ruptured IA . The incRecently, the relationship between IAs and gut microbiome has attracted a lot of attention. Gut flora has been found to assume a part in cardiovascular diseases such as atherosclerosis and hypertension , 6. HypeMendelian randomization (MR) is the use of genetic variation in non-experimental data to estimate the causal link between exposure and outcome, which can reduce the impact of behavioral, social, psychological, and other factors . Using rSNPs related with human gut microbiome were used in a GWAS. This GWAS included 18,340 individuals . This isn = 2,070) versus controls .SNPs associated with IA were extracted from a large GWAS . This GWP < 5 × 10–8) as IVs. To achieve overall results, another set of locus-wide significant(P < 1 × 10–5) SNPs was used as IVs. Second, one of the principles of the MR method: There must be no linkage disequilibrium (LD) between the selected IVs, because the existence of strong LD may lead to biased results. During our MR analysis, we reduced the LD by clumping the selected SNPs . Finally, during MR analysis, it is important to ensure that SNPs affect outcome and exposure with only one allele. According to this principle, SNPs of the palindrome structure will be removed.To confirm the causal relationship between gut microbiome and IA risk, the best IVs were selected following the following steps. A threshold of significant association with the gut microbiome was set for the selection of SNPs as IVs as the first step. We screened for SNPs with genome-wide statistical significance )/(k (1-R^2)). The number of exposure samples in the GWAS study is n, the number of IVs is k, and the degree to which IVs explain exposure is R^2. It is usually considered a weak IV when the F statistic is less than 10, which may affect the results.In MR, genetic variation is viewed as an IV, and the basic conditions for genetic variation to satisfy this IV are listed: There are no confounding factors associated with gut microbiome or IA that correlate with IVs; IVs are directly associated with gut microbiome; unless exposure is associated with the IVs, the IVs do not affect the outcome . It is cA causal link between IAs and intestinal microbes was investigated using the inverse variance weighted (IVW) method, MR-Egger, weighted median, and weighted mode. In the IVW method, the intercept term is not considered. In this method, weights are based on the inverse of variance (quadratic of standard error). A comprehensive estimate of the impact of gut microbiota on IA incidence was obtained using this method. IVW results would be highly biased if these SNPs were pleiotropic, and this must be ensured. With MR-Egger, causal estimates are unaffected by breaches of the standard IV assumptions and violations of the standard IV assumptions can be detected . WeighteAn MR-Egger regression was conducted to determine whether the SNPs included had horizontal pleiotropy. In order to monitor the presence of IVs with horizontal polymorphisms, mendelian randomized pleiotropy residuals and outliers (MR-PRESSO) was used because it had better statistical power and accuracy than MR-Egger regression. MR-PRESSO was also used to correct horizontal polymorphisms. We performed leave-one-out analysis in order to determine if causal effect estimates were reliable in the presence of potentially strong impact SNPs. We performed a leave-one-out analysis to determine if there are potentially strong impact SNPs. Thus, we are able to test whether the causal effect estimates are reliable. A further examination of the heterogeneity among selected SNPs was conducted with Cochran's Q statistics. We used the R (version 4.1.2) packages MRPRESSO and TwoSampleMR to perform MR analyses.P < 5 × 10–8) and 10,417  SNPs as IVs from a massive gut microbiome GWAS containing 211 taxa which consist of five biotypes of the genus, family, order, phylum, and class. After the removal of SNPs with LD and independent of IA, 12 (P < 5 × 10–8) and 1,291 (P < 1 × 10–5) SNPs remained as IVs. We collected important information of SNPs including beta, SE, P-value, effect allele, and other allele for further study.Firstly, we screened 461 : 0.37; 95% confidence interval (CI): 0.17—0.84, P = 0.018)] was negative with the occurrence of UIA and Sutterella  was positively related with the occurrence of UIA  was negative with the occurrence of UIA and Rhodospirillaceae  was positively related with the occurrence of UIA , Adlercreutzia  and Victivallis  were positively related with the occurrence of UIA (Supplementary Table Weighted median results of MR showed Paraprevotella and outcomes (P = 0.029), and there was no evidence of horizontal pleiotropy between other IVs and outcomes (Supplementary Table Clostridia (P = 0.359), Rhodospirillaceae (P = 0.372), Adlercreutzia (P = 0.474), Oscillospira (P = 0.137), Paraprevotella (P = 0.172), Sutterella (P = 0.201), and Victivallis (P = 0.448). Details of the instrument variables are shown in Supplementary Table Clostridia , weighted mode , weighted median  and IVW  showed that there exists no association between intestinal microbiota and UIA . Besides, F statistics were more than 10, and Cochrane Q statistics showed no significant heterogeneity (P = 0.156 for UIA). The results of the intestinal microbiota classification suggested that Streptococcus  and Peptostreptococcaceae  may increase the occurrence of UIA ,sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Rhodospirillaceae on UIA risk.Additional file 2: SupplementaryFigure 2. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Adlercreutzia on UIA risk.Additional file 3: SupplementaryFigure 3. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Sutterella on UIA risk.Additional file 4: SupplementaryFigure 4. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Victivallis on UIA risk.Additional file 5: SupplementaryFigure 5. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Oscillospira on UIA risk.Additional file 6: SupplementaryFigure 6. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of Paraprevotella on UIA risk.Additional file 7: SupplementaryFigure 7. Forest plot (A),sensitivity analysis (B), scatter plot (C), and funnel plot (D) of the causaleffect of the whole gut microbiome on UIA risk.Additional file 8: Supplementary Table 1. MR results of causallinks between gut microbiome and UIA risk (P < 1 × 10-5). Supplementary Table 2. SNPs used asinstrumental variables from gut microbiome and UIA GWASs (P < 1 × 10-5).


P = 0.03). There were no significant differences between DFT and DTR in terms of age, gender, pathological stage, preoperative body mass index, surgical bleeding, and perioperative complications. There was no statistically significant difference between the two groups in terms of reflux esophagitis and PPI intake, but DFT was superior to DTR in weight improvement at 1 year after surgery (P < 0.0001). Compared with DTR, DFT reconstruction is more demanding and time-consuming, but its postoperative nutritional status is better, so it should be the first choice for GI reconstruction in most patients with early proximal gastric cancer. However, DTR should be the best choice for patients who have difficulty operating.Surgical resection is the main treatment for proximal gastric cancer, but there is no consensus on its reconstruction. We carried out a meta-analysis to evaluate the effects of double-tract reconstruction (DTR) and double-flap technique (DFT) on postoperative quality of life in patients with proximal gastric cancer. Systematic searches of PubMed, Web of Science, EBSCO, and the Cochrane Library were performed. Literature for the last 5 years was searched without language restrictions. The cutoff date for the search was 12 April 2023. Literature and research searches were conducted independently by two researchers and data were extracted. Statistical analyses were performed using Review Manager (Revman) 5.4 software. Fixed models were used when heterogeneity was small and random-effects models were used for meta-analysis when heterogeneity was large. The study was registered with PROSPERO, CRD 42023418520. Surgical time was significantly shorter in the DTR group than in the DFT group (The online version contains supplementary material available at 10.1007/s13304-023-01638-w. Gastric cancer is one of the top five cancers in the world. Although the overall incidence of gastric cancer has been decreasing in recent decades, the incidence of proximal gastric cancer is on the rise, especially in Asian countries . SurgeryDFT is an anastomosis method with anti-reflux mechanism, but anastomotic stenosis is one of its main complications . DTR is The diagram of digestive tract reconstruction after PG is shown Fig. .Fig. 1DiThis study was based on the PRISMA 2020 Statement: Guidelines for Updating Systematic Review Reports . A systeInclusion criteria: (1) clinically and pathologically confirmed as upper gastric cancer or Siwet II/III AEG; (2) cTNM stage I or II; (3) comparative studies of PG-DTR and PG-DFT; (4) the outcomes including basic information, perioperative status, and 1-year follow-up.Exclusion criteria: (1) PG-DFT and PG-DTR reconstruction methods were not included in this study; (2) conference abstracts, case reports, reviews, commentaries, letters, meta-analyses, or animal studies; (3) patients with serious underlying medical conditions that may affect treatment selection and outcomes.A total of 1646 articles were retrieved from PubMed, Embase, and Cochrane Library. Five studies that met the inclusion criteria were finally included in this study. The flow screening process is shown in Fig. Data refinement included: (1) research background ; (2) cohort characteristics ; (3) perioperative outcomes ; (4) postoperative complications ; (5) nutritional status 1 year after operation  level).The primary outcomes of this study were postoperative nutritional status, defined primarily as BMI or Hb level at 12 months postoperatively and reflux esophagitis at 12 months postoperatively. Secondary outcomes were surgical outcome, including operation time, surgical bleeding, and total perioperative complications.The assessment for inclusion in this study was done independently by two researchers. In case of disagreement, the decision will be made after discussion. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of the controlled clinical trial (CCT). The scale consisted of study population selection (4 items), comparability between groups (2 items), and outcome indicators (3 items). Each score is 1 point, more than 6 points for a high-quality CCT, and up to 9 points .The funnel plot of the standard error of the total complication rate was used to evaluate the publication bias of this map. In the absence of publication bias, it is assumed that high-precision studies will be drawn near the average , and low-precision studies will be evenly distributed on both sides of the vertical line to form a funnel-shaped distribution.p value less than 0.05 was considered significant. Clinical outcomes and complications were analyzed using mean weight difference (WMDs), odds ratio (ORs), and 95% confidence interval (CI). P 0.1, I2 ≤ 50%. If there was no heterogeneity between studies, a fixed-effect model was used. If heterogeneity existed, a random-effects model was used.Statistical analyses were performed using Review Manager 5.4 software. Continuous variables were expressed as mean ± standard deviation (SD), or median and normal range. Categorical variables were expressed as number and percentage. A A total of 1646 studies were retrieved, with 926 studies remaining after eliminating duplicate results. In addition, a total of 720 unrelated studies, 35 case reports, 60 meta-analyses, 34 reviews and commentaries, and 77 remaining studies were identified by searching the titles and abstracts of articles. Full-text retrieval, excluding 41 comparative studies with TG and 31 data studies that did not meet the requirements of this study, the remaining 5 were all included in the study  and in patients with DTR (n = 199). The DTR group was shorter than the DFT group, and operative time was recorded in four of five studies, including DFT (n = 160), and DTR (n = 199). The difference was not statistically significant (P = 0.03) according to the random-effects model test  [Z = 1.22 (P = 0.03)].  and DTR (n = 92). There was no significant difference between DFT and DTR in terms of surgical bleeding. A random-effects model  [Z = 1.22 (P = 0.22)] was used  patients and DTR (n = 213) patients. A fixed-effects model [Z = 0.77 (P = 0.44)] was used because of strong homogeneity , and the results showed no significant difference between the two , so we used random effect model for the study [Z = 0.06 (P = 0.95)]. The results showed no significant difference between DFT and DTR  and in patients with DTR (n = 73). A fixed-effects model was chosen for the analysis, because of  [Z = 1.05 (P = 0.30)], and it showed no statistical significance in PPI intake between DFT and DTR  and DTR (n = 213). However, only two studies  . Fixed-effect model was selected for this meta-analysis  [Z = 15.44 (P < 0.0001)] ] Fig. A. Howeven = 126) and DTR (n = 172). Both were significantly different between DFT and DTR. Preoperative Hb was modeled using a fixed-effects model  [Z = 9.02 (P < 0.0001)]  [Z = 9.02 (P < 0.0001)] ] ] Figs. c. In pre1)] Fig. C. In Hb P value was 0.73 indicating no significant publication bias.The symmetry of the funnel plot Fig.  with theP = 0.03). This is because DFT anastomotic embedding requires manual suturing, whereas DTR has three anastomoses but is now basically anastomosed with an anastomosis and then manually reinforced. In our study, there was no significant difference between DFT and DTR in terms of reflux esophagitis and PPI uptake. The difference in Hb levels between preoperative and 1-year postoperative was not statistically significant, but the 1-year postoperative BMI results suggested that the nutritional status of DFT may be better than that of DTR 1-year postoperatively.In this study, we systematically reviewed the studies of DFT and DTR, and performed a meta-analysis of five retrospective controlled clinical trials of DFT and DTR. As we know, this study is the first meta-analysis comparing the outcomes of DFT and DTR after PG. The focus was on the surgical outcome, the incidence of postoperative reflux esophagitis, and the postoperative nutritional status of the two reconstruction methods. We concluded that there was no significant difference between DFT and DTR in terms of age, gender, pathological stage, preoperative body mass index, intraoperative blood loss, and perioperative complications. However, the difference in operative time between the DFT and DTR groups was statistically significant (P = 0.177). The DTR group had a significantly lower body weight (P = 0.038) and body fat (P = 0.009). Although postoperative nutritional indicators were different and could not be compared by data, four of the five studies considered DFT to be associated with better postoperative nutritional status, apart from one of the five studies that lacked comparative data.From the above results, DFT and DTR are similar and acceptable in terms of the feasibility and safety of surgery. However, postoperative nutritional status, especially postoperative weight changes, showed better results with DFT. Nishimura et al.  showed tTo parse these results, it is possible that all food in the postprandial DFT passes through the remnant gastroduodenal pathway into the jejunum, whereas in the DTR only part of the food passes through the remnant gastroduodenal pathway and the rest of the food passes through the middle jejunum pathway into the jejunum. Food that passes exclusively through the gastroduodenal route may have advantages in digestion and absorption. Takase et al.  concludeThe incidence of gastric cancer is among the top five in the world and mortality rate is among the top three . AlthougThe anti-reflux anatomy of the esophagogastric junction consists mainly of the cardia and angle of His, but separation of the vagus nerve during proximal gastrectomy increases the incidence of pyloric spasm and impaired emptying of the remnant stomach . Some paAlthough our results show that DFT may be the first choice for GI reconstruction in most patients with early proximal gastric cancer, there are still some limitations. First, only five studies were included in this meta-analysis, with a small total sample size. Second, the main comparative indicators, such as the selection and comparison of postoperative nutritional indicators, were different, resulting in less comparative data available for this study. The studies included in this study were retrospective studies with poor quality evidence. Finally, when comparing different surgical approaches, tumor safety is a priority. However, none of the included studies had long-term follow-up of survival. Future large multi-center prospective randomized controlled studies are needed to compare the role of DTR and DFT in long-term follow-up.Supplementary file1 (DOCX 30 KB)Supplementary file2 (DOCX 23 KB)Below is the link to the electronic supplementary material.