Clinical events suggestive of nutrition care found in electronic health records (EHRs) are rarely explored for their associations with hypertension outcomes.n = 4,237) tested for associations between last visit blood pressure (BP) control (≤ 140 Systolic BP and ≤ 90 Diastolic BP) and ≥ 1 nutrition care clinical event operationalized as  diagnoses, preventive care visits, or provision of patient education materials (PEM)). Descriptive statistics and longitudinal targeted maximum likelihood estimation (LTMLE) models were conducted to explore average treatment effects (ATE) of timing and dose response from these clinical events on blood pressure control overall and by race.Longitudinal analysis using structured EHR data from primary care visits at a health system in the US from December 2017—December 2020 of adult patients with hypertension (p = 0.003), preventive visits in the last 2 years high higher odds for BP control , and early or late PEMs had lower odds for BP control .The median age was 62 years, 29% were male, 52% were Black, 25% were from rural areas and 50% had controlled BP at baseline. Annual documentation of overweight/obesity diagnoses ranged 3.0–7.8%, preventive care visits ranged 6.2–15.7%, and PEM with dietary and hypertension content were distributed to 8.5–28.8% patients. LTMLE models stratified by race showed differences in timing, dose, and type of nutrition care. Black patients who had nutrition care in Year 3 only compared to none had lower odds for BP control (ATE -0.23, 95% CI: -0.38,-0.08, In this study, clinical events suggestive of nutrition care are significantly associated with BP control, but are infrequent and effects differ by type, timing, and patient race. Preventive visits appear to have the most effect; additional research should include examining clinical notes for evidence of nutrition care among different populations, which may uncover areas for improving nutrition care for patients with chronic disease.The online version contains supplementary material available at 10.1186/s12911-023-02311-3. High blood pressure (BP), or hypertension, affects nearly 1 in 3 US adults . A varieProviding nutrition care may improve patient self-management and hypertension outcomes overall , 9, but Little is known about the rates of nutrition care events documented for hypertension management or their relationship with BP control of patients. Given this, the objectives of this study were to assess of rates of nutrition care events identified in structured EHR data and to test whether the timing and dose of these were associated with BP control for adult patients in an academic health system. The hypothesis tested was that documented nutrition care, controlling for patient demographic and health characteristics, is associated with BP control.n = 43,246) between December 2017 and December 2020 for  adult patients, age 18 to 85 years at the date of their last BP measurement, who had their first visit prior to 1/1/2019 with a recorded BP measurement, at least two primary care visits during the study period and had a previous diagnosis of hypertension. Records of patients with chronic kidney disease, pregnancy, or who were in hospice or long-term care were excluded per the clinical quality measure for controlling high BP [A single, safety-net academic medical center with six primary care clinic sites in the Mid-Atlantic US serves a diverse patient population of both rural and urban, and underrepresented patients. Deidentified EHR data were obtained for clinical visits ( high BP . Patient high BP .The outcome of interest was BP control (yes/no), defined as ≤ 140 mm Hg systolic BP (SBP) and ≤ 90 mm Hg diastolic BP (DBP) per the National Committee for Quality Assurance (NCQA) quality measure for “Controlling High Blood Pressure”. This outcome was calculated at the patients’ first visit and annually based on the last measured BP in the calendar year. BP control values were carried forward if they were not updated in subsequent visits.Three commonly provided services in primary care hypertension management were used as a proxy for nutrition care, justified by the assumption that nutrition-related information was exchanged with the patient. These nutrition care events were exclusive of the final visit and identified by diagnosis and billing codes for overweight/obesity diagnoses and preventive visits, and a flag that diet-related education materials were provided to the patient within the study period. Clinical guidelines for the treatment of overweight/obesity include dietary behavior management , 21, andDescriptive statistics  were calculated for all patients’ and stratified samples of Black and white patients’ demographic characteristics and hypertension-relevant indicators, proportions of patients with controlled BP, and rates of documented nutrition care events.Longitudinal Targeted Maximum Likelihood Estimate (LTMLE) , 25 is ap-values for each LTMLE model with alpha 0.05. Comorbidities were calculated with HCUP Elixhauser software [Results are presented as average treatment effect parameter estimate differences (ATE), 95% confidence intervals, and software  program n = 4,237) was 62 years , nearly a third  were male, half  were Black/African American, 25.4%  were from rural areas, and 7.9% (n = 333) were covered by Medicaid insurance. Most patients in the sample were overweight or obese  for at least one recorded BMI during the study period. The median total number of anti-hypertensive prescriptions per patient over the study period was 6 . About a third  had one or more comorbidities, and less than half  had controlled BP at their first recorded BP during the study period.Descriptive statistics for patients’ characteristics and clinical factors are found in Table n = 533 (16.4%) to n = 1,855 (43.8%); for Black patients: n = 125 (7.6%) to n = 617 (28.1%); and for white patients: n = 153 (9.5%) to n = 602 (29.5%)). Overweight/obesity diagnoses were recorded for far fewer patients annually across the study period  to n = 329 (7.8%); for Black patients: n = 61 (3.7%) to n = 210 (10.3%); and for white patients: n = 37 (2.3%) to n = 125 (6.1%)). Ranges of documented preventive visits were overall: n = 203 (6.2%) to n = 664 (15.7%); for Black patients: n = 85 (5.1%) to n = 319 (14.5%); and white patients: n = 118 (7.4%) to n = 345 (16.9%).Table p = 0.03 and ATE -0.23, 95% CI: -0.38,-0.08, p = 0.003, respectively). Having a nutrition care event in both years 1 and 3 compared to none was positively associated with BP control  among Black patients, however.Estimates of average treatment effects (ATE) on BP control for any nutrition care event, at least one of preventive care visits, obesity/overweight diagnosis, or provision of PEMs at different timing intervals – Year 1 (Early), Year 3 (Late) – compared to none of these clinical visits are presented in Table p = 0.01). Similarly, preventive visits in only year 3 versus non among white patients had a positive effect on BP control . Obesity/overweight diagnoses during both years 2 and 3 versus none among white patients had the greatest effect on BP control in the study . Patient Education materials early (year 1) or late (year 3) versus none both had negative and significant associations with BP control for the full sample . This was also true among Black patients .Preventive visits in years 2 and 3 versus none among Black patients had a positive effect on BP control , clinics were successful in using the tool to support clinicians to counsel patients about health behaviors and customize prevention and treatment plans for patients . Such inFindings of this study offer new contributions and suggestions for additional work needed within the burgeoning area of health services research that seeks to improve preventive services to support patients with chronic disease. First, due to our limited established structures to measure or examine nutrition-related activities in primary care, this study provides a framework of proxy measures for preventive nutrition care that may be found in the voluminous EHR data. Next, this study applied longitudinal analyses in stratified samples of underrepresented racial and ethnic patients, with significant findings to support conducting further detailed explorations of causes and ways forward for improvement. Although not part of the present study, additional stratification by comorbidities may be conducted to assess differences in treatment plans and nutrition care for complex patients. To gain more insight into nutrition care services and relevant patient outcomes, future research should use a larger data sample or data from a group of health systems, and additional data sources e.g., clinical notes for preventive counseling; and claims data for clinical referrals to dietitians are other avenues to offer a more robust picture of successful processes for conducting and documenting nutrition care delivery that might reveal targets for improvements.Our study has important limitations. Using EHR data for research has known challenges due to variability of data entry . As a siThe present study utilized EHR data to provide a description of nutrition care delivery and examination of its association with patient BP outcomes within a single health system. Overall, documentation of received nutrition care events was low, and preventive care visits, but not overweight/obesity diagnosis or delivery of patient education materials, was associated with patients’ BP control. Additionally, disparities were identified in rates of nutrition care events and odds for BP control by race. Further research is needed to explore ways to improve documentation and equity of nutrition care. Enhancing EHR workflows, education for providers and staff about nutrition care, and improving effective communication and collaboration within the clinical team may all be system-level targets for improving nutrition care and hypertension outcomes.Additional file 1.


Recently it was suggested that urine albumin‐to‐creatinine ratio (uACR), even within the normal range, can be associated with hypertension, but only a few studies have examined. Therefore, this study aimed to determine the association between normal range uACR and the prevalence of hypertension.The research used data from the 2009 to 2018 National Health and Nutrition Examination Survey, which included 14,919 participants. We defined the uACR as the amount of albumin (mg/dL) divided by creatinine (g/dL) in randomly voided urine. Hypertension was defined as mean systolic blood pressure ≥130 mmHg, or diastolic ≥80 mmHg, or were taking hypertension medication or were informed of a hypertension diagnosis by a physician/health professional.p for nonlinearity<.001). In addition, in the subgroup analysis stratified by body mass index, the lower the BMI, the stronger the association between uACR and hypertension prevalence.In multivariable‐adjusted models, per 5 mg/g uACR increment, the hypertension prevalence increased 1.31‐fold , the odds [95% confidence interval (CI)] for hypertension prevalence were 2.25 (1.86–2.72) for those in the highest quartile compared to those in the lowest quartile. The nonlinear relationship between hypertension prevalence and uACR was found by visually assessing images (Even within the normal range, subtly elevated uACR was associated with an increased prevalence of hypertension in the USA general population, and this association may be enhanced in individuals with low BMI. Further research is needed to assess the clinical applicability of these findings. This study assessed the association between uACR levels and the prevalence of hypertension in adults in the United States, using data from NHANES 2009–2018. To conclude that even within the normal range, subtly elevated uACR was associated with an increased prevalence of hypertension in the USA general population, and this association may be enhanced in individuals with low BMI. We also looked at whether the association varies by participant characteristics like age, gender, BMI, behavioral risk factor, and comorbidities, which could help with future clinical management of uACR.22.1The Centers for Disease Control and Prevention (CDC) of America conducts the NHANES on a 2‐year cycle, participants are noninstitutionalized individuals from the United States who are chosen through a complex stratified, multistage sampling design. In the current study, we used data from five NHANES cycles  to investigate the association between uACR and blood pressure among NHANES participants. All information was obtained from the Public Data General Release file documents. The National Center for Health Statistics Ethics Review Board approved the NHANES, and all participants provided written informed consent before completing the NHANES.In the present study, we analyzed NHANES participants (age ≥20 years) from five cycles of NHANES 2009–2018), data on demographics, exams, lab tests, and questionnaires were gathered. Participants who have incomplete data on laboratory urine data, blood pressure, and pregnant women were excluded, participants had missing demographic data and other covariates data also excluded. After exclusions, this study contained a total of 14 919 participants aged ≥20 years with normal uACR   to the laboratory. The sample's stability was demonstrated at 5°C and temperatures less than or equal to −20°C.2.3The main outcome variable, blood pressure (BP), was measured with a mercury sphygmomanometer by trained personnel following standardized protocols,All systolic and diastolic blood pressure measurements were taken at the Mobile Examination Center. In the present study, we calculated the average of systolic and diastolic BP readings for further analyses, if they had only one BP reading, then, it was the final record. Hypertension was defined as a mean SBP ≥130 mmHg, or a mean DBP ≥80 mmHg, or were taking hypertension medication or were informed of a hypertension diagnosis by a physician/health professional.2.42), over‐weight (25–29.9 kg/m2), and obese (≥30 kg/m2). Laboratory tests include Uric Acid , total cholesterol , and estimated glomerular filtration rate . Assessments of behavioral risk factors included smoking, drinking, and physical exercise. Smoke exposure is measured by the level of serum cotinine .Demographic characteristics included age , gender , race/ethnicity , levels of education , poverty income ratio . Dietary information on total sodium and total energy intake was collected by trained interviewers. Body mass index (BMI) categorized as under/normal weight . The covariate adjustment was determined by the following principle: when covariates were added to this model, the matched odds ratio changed by at least 10%. P for trend tests were performed by rerunning the corresponding regression models with the quartiles of uACR as a continuous variable. In addition, to characterize the shape of the relationship between uACR and the main outcome, a generalized additive model and fitted smoothing curve were used. The log‐likelihood ratio test was used to determine whether a threshold exists by comparing a one‐linev (nonsegmented) model to a segmented regression model. The inflection point connecting the segments was determined using two‐step recursive methods based on the model with the highest likelihood. Subgroup analyses were carried out using stratified linear regression models to detect effect modification.The participants were characterized using descriptive statistics, where continuous variables were expressed as mean standard deviation and categorical variables as frequency or as a percentage. The one‐way ANOVA  and Kruscal–Wallis H (skewed distribution) tests were used to compare continuous variables between the various groups. The http://www.R-project.org, The R Foundation). p < .05 (two‐sided) were considered statistically significant.According to recommendations from the National Center for Health Statistics, appropriate sampling weights  were created to take into consideration the complicated survey design and produce nationally representative estimates.3p < .001).We included 14 919 participants in our analysis. The average age of the participants was 49.7 ± 17.6 years, with a male versus female ratio (49.02% vs. 50.65%). The median uACR of the participants was 6.3 mg/g . The weighted prevalence of hypertension was 35.8%. The baseline characteristics of participants according to uACR level from the NHANES (2009–2018) are shown in Table β: 2.14; 95% CI 1.78–2.47) increased by 2.14 mmHg, diastolic blood pressure  increased by 0.73 mmHg, and the hypertension prevalence increased 1.31‐fold . When continuous uACR was converted to quartiles, within the normal uACR range, the highest uACR quartile group had a 6.46 mmHg increase in systolic blood pressure , a 2.63 mmHg increase in diastolic blood pressure  and the risk of hypertension . increased 2.25‐fold compared to the lowest quartile group. There was a trend for higher β of blood pressure and OR of hypertension among participants in the higher quartile of uACR relative to the lower quartile (p for trend <.001).Table p for nonlinearity<.001), further analysis found that the inflection point of the threshold effect was 7.65 mg/g of uACR, below the threshold, the prevalence of hypertension increased significantly for each 1 mg/g increase in uACR  and then slowly increased above the threshold .uACR and the prevalence of hypertension were positively correlated, according to the generalized additive model's results and fitted smoothing curve Figure . The nonp for interactions = 0.012), other than BMI, age, gender, smoking status, drinking status, physical activity and diabetes did not significantly change the association between uACR and hypertension prevalence .A stratified analysis of participants was performed to assess the relationship between uACR (continuous variable) and hypertension in various subgroups Figure . An inte4The present study utilized the population‐based cross‐sectional resources of NHANES to detect the correlation between uACR levels and prevalence of hypertension in adults, which, to our knowledge, was the first time to examine such a relationship in this population. We found that uACR within the normal range was positively correlated with systolic and diastolic blood pressures and the prevalence of hypertension even after multivariable adjustment. The nonlinear relationship between hypertension prevalence and uACR was found by visually assessing images. The optimal cutoff point of the association of uACR with hypertension was 7.65 mg/g, on each side of the optimal uACR value, the magnitude of the correlation between uACR and the prevalence of hypertension was different. Furthermore, the stratified analysis showed that the association between uACR levels with hypertension was much stronger among nonobese individuals compared with obese people.Although the mechanisms underlying the association of uACR with hypertension are largely unknown, there are some possible explanations. Systemic and glomerular vascular endothelial dysfunction may be a potential physiological link between albuminuria and hypertension.There has been growing evidence in recent years that urine albumin excretion, even when it is within the normal range, is linked to an increased risk of hypertension. The Nurse's Health Studyp for interactions = .012). However, our data do not suggest that uACR can more accurately identify those at high risk of incident hypertension among nonobese individuals. Concerns have been raised that interindividual differences in muscular mass have a significant influence on the uACR value via urinary creatinine excretion, that the uACR assessment overestimates urine albumin excretion in people who have low muscle mass, and therefore may not be associated with vascular disease.Furthermore, the stratification analyses of age, gender, smoking status, drinking status, physical activity, and diabetes were conducted, and no significant interaction was found. This positive association persisted across subgroups stratified by these factors, demonstrating the robustness of our findings and increasing our confidence in the reliability of the results. But notably, in our BMI‐stratified subgroup, nonobese individuals showed a stronger association between uACR levels and hypertension than obese individuals ; data acquisition (lead); data curation ; data analysis ; methodology (lead); writing—original draft ; writing—review & editing (lead). Duan Wang: Protocol development (lead); data acquisition ; data curation ; data analysis ; methodology (lead); writing—original draft (lead); Writing—review & editing (lead). Yong Zhu: Protocol development (lead); data acquisition (lead); data curation (lead); data analysis ; methodology (lead); Writing—original draft (lead); Writing—review & editing (lead).The authors declare no conflict of interest.


Oryza sativa was grown for a long period of time, converted to Zea mays after a year, and then Glycine max was planted. The results showed that different plant cultivations in a paddy–dryland rotation system affected soil physicochemical properties and enzyme activity, and G. max field cultivation resulted in higher total carbon, total nitrogen, soil total organic carbon, and available nitrogen content while significantly increasing α–glucosidase, β–glucosidase, and alkaline phosphatase activities in the soil. In addition, crop rotation altered the r/K–strategist bacteria, and the soil environment was the main factor affecting the community structure of r/K–strategist bacteria. The co–occurrence network revealed the inter–relationship between r/K–strategist bacteria and fungi, and with the succession of land rotation, the G. max sample plot exhibited more stable network relationships. Random forest analysis further indicated the importance of soil electrical conductivity, total carbon, total nitrogen, soil total organic carbon, available nitrogen, and α–glucosidase in the composition of soil microbial communities under wet–dry events and revealed significant correlations with r/K–strategist bacteria. Based on the functional predictions of microorganisms, wet–dry conversion altered the functions of bacteria and fungi and led to a more significant correlation between soil nutrient cycling taxa and environmental changes. This study contributes to a deeper understanding of microbial functional groups while helping to further our understanding of the potential functions of soil microbial functional groups in soil ecosystems.Soil microbial taxa have different functional ecological characteristics that influence the direction and intensity of plant–soil feedback responses to changes in the soil environment. However, the responses of soil microbial survival strategies to wet and dry events are poorly understood. In this study, soil physicochemical properties, enzyme activity, and high–throughput sequencing results were comprehensively anal0079zed in the irrigated cropland ecological zone of the northern plains of the Yellow River floodplain of China, where  Soil microorganisms play a critical role in regulating soil ecological processes and biogeochemical cycles and participate in and mediate plant–soil feedback (PSF) processes ,2. This Zea mays (dryland) and Oryza sativa (wetland) cultivation in the Yellow River floodplain wetlands can help predict agroecosystem responses to current and future environmental changes.Meanwhile, changes in the structure and function of soil microbial communities involved in biogeochemical cycles under wet–dry events have received increasing attention ,15,16. AIn addition, we were interested in the survival strategies of microorganisms during wet and dry events. Specifically, different microbial taxa exhibit different ecological characteristics ,20. For O. sativa planting) and drylands (O. sativa fields converted to Z. mays and Glycine max fields for one year) in floodplains in Ningxia through the high–throughput sequencing of soil microorganisms and the determination of soil physicochemical properties. The following questions were addressed: (1) How do soil microbial diversity and r– and K–strategists bacteria respond to plant–soil feedback under wet–dry events? (2) How do soil bacterial and fungal functions respond to wet–dry events?Although the inter–relationship between spatial variation in environmental factors and PSF is controversial, factors related to climate change  act as drivers that influence soil microbes, thereby influencing soil carbon and nutrient cycling ,25,26. Ihttps://apps.nationalmap.gov/viewer/ (accessed on 17 October 2023). In this study, O. sativa was grown for eight years, and the soil samples were named O. sativa–planting soil (RPS); the O. sativa field was then replaced with a Z. mays field for one year, and soil samples were named Z. mays–planting soil (MPS); then, the O. sativa field was changed to a Z. mays field for one year and then G. max was planted for one year, and soil samples were named G. max–planting soil (SPS). Three sample plots  were divided into nine quadrats, each covering an area of approximately 660 m2. Five sampling points were assigned randomly to each quadrat [The study site was located in Xingfu Village, Helan County, Ningxia  and was part of the plain–irrigated cropland ecological zone of the middle and upper reaches of the Yellow River . The fig quadrat ,31. PlanTo reduce the effect of moisture on the soil microbial community structure, we used the method described by Qi et al. (2020) in which MPS and SPS sample soils (50 g) were placed in 200 mL glass bottles, and then sterile water was added to 100% field water capacity (FWC), which was sealed and sterilized together with the RPS sample soil, and cultured in a dark room (20 °C) to stabilize microbial communities . The soiThe 27 soil samples were sieved and weighed to determine the soil water content (SWC). Briefly, 10 g of soil was weighed in a beaker, 50 mL of deionized water was added, and a conductivity meter  was used to determine the soil electrical conductivity (EC), and a pH meter  was used to determine the soil pH . Soil saFresh soil samples were naturally air–dried, and 1 g of soil samples was weighed, added to toluene extraction, and colorimetrically measured with MUB buffer solution  to determine the activities of 1,4–α–glucosidase (αG), 1,4–β–glucosidase (βG), 1,4–β–xylosidase (βX), phenol oxidase (POX), β–1,4–Nacetyl–glucosaminidase (NAG), leucine aminopeptidase (LAP), and alkaline phosphatase (SAP) ,34. We uSoil DNA was extracted from the 27 soil samples using the CTAB method. The soil bacterial V3–V4 gene region and fungal ITS1 were amplified using primers  ,37. AfteQIIME (V1.9.1) software was used to analyze microbiome alpha diversity  . The Brap < 0.001) and then established the co–occurrence network with established data  [To visualize the relationship between r/K–strategist bacteria and functional fungi more intuitively, we calculated the Spearman coefficients for the OTUs of r/K–strategist bacteria and fungi in the three sampling plots  . We furtd fungi) . p < 0.05). The r/K–strategist bacteria with differential bacterial functional groups were correlated and presented using the Cytoscape software (3.7.1) [We further analyzed the elemental cycling function of the bacterial communities and predicted it using FAPROTAX . The bac (3.7.1) . Further (3.7.1) , and SpeZ. mays and G. max planting significantly increased soil EC, while TC, TN, TOC, and AN contents were significantly higher in plots after G. max planting than in the RPS and MPS sample plots (p < 0.05). Soil αG, βG, and NAG contents were higher in the SPS sample plots than in the RPS and MPS sample plots, whereas LAP was significantly lower than RPS and MPS (p < 0.05)  .Z. mays cultivation increased the alpha diversity of the soil bacteria. The wet–dry events had no significant effect on soil fungal diversity but decreased richness (p < 0.05)  A,B. The  < 0.05) C,D. Corr < 0.05) E. p < 0.05)  C. The Ma < 0.05) D. G. max planting. The ratio of positive–to–negative edges in the SPS plot was higher than those in the RPS and MPS plots, and the number of modules in the SPS plot was also higher. By constructing a functional fungal network, Gammaproteobacteria, Alphaproteobacteria, and Acidobacteriota were found to vary similarly in the bacterial–fungal network   .Z. mays and G. max cultivation requires water availability, despite being in a dryland agroecosystem [O. sativa–growing fields indirectly reduces the enrichment of soluble cations in the soil, thus decreasing the soil EC. The TC content of the soil decreased and then increased with the O. sativa–Z. mays–G. max rotation, showing significant differences between the sample plots. Wet soils showed increased soil carbon mineralization and TC content, which explains the higher TC content of the MPS sample plot than that of the RPS sample plot in this study [O. sativa cultivation [The intensity of the transition from wet to dry soil generally leads to changes in pH . Howevercosystem . Moreoveis study . The higtivation . O. sativa cultivation is the main source of N2O, especially in wet–dry events. However, the increase in soil organic carbon mineralization through the wet–dry farming of soil could enhance the accumulation of nitrogen [G. max field was not only caused by the increased TOC content but also by the biological nitrogen fixation ability of legumes on soil TN and soil nitrogen availability [O. sativa–Z. mays–G. max rotation practice, resulting in insignificant changes in soil TP and AP content [The changes in TN content showed a pattern similar to that of TC. nitrogen ,50. Furtlability . It has lability . Furtherlability . This st content . Another content .Numerous studies have concluded that high TC content positively affects soil extracellular enzyme activity in addition to increasing soil carbon and nitrogen availability ,55. In tLand–use changes and wet–dry events not only affect soil nutrient availability but also affect microbial community diversity . In our Recent studies have found that, as soil organic carbon and nitrogen stocks increase, they increase the proportion of K–strategists and decrease the proportion of r–strategists . Our finZ. mays cultivation increased the connectivity and complexity of the network (with more nodes and edges), whereas nutrient cycling under wet–dry events changed the interaction and intensity of r–strategist bacteria and fungi, thus affecting the network relationships [Reciprocal and competitive relationships among soil microorganisms can also be characterized using co–occurrence networks . In our ionships . In addiionships . Althougionships ,66. In cionships .The impact of agricultural activities on nutrient accumulation in soil ecosystems shapes soil microbial communities and alters their functions ,68. In tIn view of the ecological indicator role of saprotroph in land–use conversion , a signiG. max field cultivation resulted in higher TC, TN, TOC, and AN content while also significantly increasing αG, βG, and SAP activity in the soil. In addition, crop rotation altered the r/K–strategist bacteria, and the soil environment was the main factor affecting the community structure of r/K–strategist bacteria. The co–occurrence network revealed the inter–relationship between r/K–strategist bacteria and fungi, and with the succession of land rotation, the G. max sample plot exhibited more stable network relationships. Random forest analysis further indicated the importance of EC, TC, TN, TOC, AN, and αG in the composition of soil microbial communities under wet–dry events and revealed significant correlations with r/K–strategist bacteria. Based on functional predictions of microorganisms, wet–dry conversion altered the functions of bacteria and fungi and led to a more significant correlation between soil nutrient cycling microbial taxa and environmental changes. This study contributes to a deeper understanding of microbial functional groups; however, this is only limited to the Yellow River beach area in northwestern China, and it is hoped that future studies can be carried out on a larger scale to better understand the potential functions of soil microbial functional groups in soil ecosystems.In conclusion, the results of this study showed that different plant cultivations in a paddy–dryland rotation system affected soil physicochemical properties and enzyme activity. Moreover, the


Model predictions show that the average density of the palm was 32% greater while the canopy height was 20% shorter in forests exposed to the two storms relative to unexposed areas. Our results demonstrate that hurricanes have lasting effects on forest canopy height and composition, suggesting the expected increase in hurricane severity with a warming climate will alter coastal forests in the North Atlantic.Projected increases in hurricane intensity under a warming climate will have profound effects on many forest ecosystems. One key challenge is to disentangle the effects of wind damage from the myriad factors that influence forest structure and species distributions over large spatial scales. Here, we employ a novel machine learning framework with high‐resolution aerial photos, and LiDAR collected over 115 km Projected increases in hurricane intensity under a warming climate will have profound effects on many forests. We employ a novel machine learning framework with high‐resolution aerial photos and LiDAR collected over El Yunque National Forest in Puerto Rico to examine the effects of hurricanes on the current canopy height and density of Prestoea acuminate, a wind‐resistant palm. Model predictions show that the average density of the palm was 32% greater while the canopy height was 20% shorter in forests exposed to the two storms relative to unexposed areas. Nevertheless, it still remains a challenge to analyze these data in a scalable, distributed, and reproducible workflow. Here, we employ a novel machine learning framework for weakly supervised image categorization , Palo Colorado forest from about 600 to 900 m (dominated by Cyrilla racemosa), Sierra palm forest, dominated by Prestoea acuminata, found above 500 m, and elfin woodland above 900 m  aerial photos from NASA Goddard's Lidar, Hyperspectral, and Thermal (G‐LiHT) Airborne Imager  collected in 2016 provided ground observation data for labeling and validation of species' distributions derived from G‐LiHT fine‐scale (3 × 3 cm) aerial imagery of the rainforest Figure .2.2.2https://glihtdata.gsfc.nasa.gov/.Canopy height at a 5 m × 5 m resolution was derived from NASA G‐LiHT LiDAR data  with a 5 m pixel resolution.2.2.4https://coast.noaa.gov/digitalcoast/data/hurricanes.html).To reconstruct wind exposure in the EYNF, we used EXPOS, a simple model that combines information on the track of a hurricane, wind speeds, and topography to predict heterogeneity in wind impacts across the landscape , and applied it to obtain pixel‐wise density predictions for 2.3.2P. acuminata across the forest. Before analysis, we aggregated all the data to the 1‐ha scale. This aggregation minimized fine‐scale noise and facilitated computation. For continuous variables , we averaged the values of all the 5 m × 5 m pixels within each hectare, and for discrete covariates (geology), we used a majority vote. To transform continuous density predictions at the 3 cm × 3 cm scale for the target species into a binary output (species present or absent), we chose an optimal cut‐off. We first visualized the curves of IoU‐versus‐cut‐off and chose the cut‐off values that yielded the highest IoUs  between wind exposure derived from the EXPOS model and the two topographic variables included in the model, elevation and slope, were low (<.25). To assess potential collinearity issues, we also ran a VIF analysis on a general linear model with all covariates included in the model before we fitted the spatial model. All VIFs were <5, demonstrating that collinearity was not an issue in the analysis.The diversity of forest conditions across the EYNF, as sampled by the aerial photographs and LiDAR, provides a unique opportunity to examine the factors, including exposure to past hurricanes, that drive variation in canopy height and density of spatialreg , both, or none. We used this same approach to assess the loss of predictive power (Nagelkerke R2) for models with and without hurricanes. All the statistical analyses were carried out in R 4.1.2  shorter in areas exposed to H. Hugo and 14.23% (13.77% and 14.69%) lower in areas exposed to H. Georges relative to areas protected from the storms. Overall, canopies were 20% (19.73% and 20.67%) shorter in areas exposed to both storms than in protected areas  higher in areas exposed to both H. Hugo and Georges relative to unexposed areas  effects of severe winds on canopy damage ; formal analysis ; funding acquisition ; methodology ; supervision (lead); visualization ; writing – original draft (lead). Chengliang Tang: Data curation ; formal analysis ; investigation ; methodology ; visualization ; writing – review and editing . Douglas C. Morton: Data curation ; funding acquisition ; writing – review and editing . Tian Zheng: Formal analysis ; supervision ; writing – review and editing . Jess K. Zimmerman: Data curation ; funding acquisition ; writing – review and editing .The authors declare no competing interests.


Type 2 diabetes mellitus (T2DM) and diabetic complications threaten human health seriously. Healthy lifestyles can lower the risk of cardiovascular disease (CVD) and long‐term complications. However, the relationship between alcohol consumption and CVD mortality is still controversial, and there is a lack of evidence from large‐scale longitudinal studies in the Chinese population. Based on the REACTION study , this paper explores the association between alcohol consumption and all‐cause mortality, stroke, and coronary heart disease (CHD) in patients with abnormal glucose metabolism during a 10‐year follow‐up period to provide evidence for lifestyle counselling for these patients.p value < 0.05 was considered statistically significant.First, baseline data were collected from the REACTION study cohort in Changchun, Jilin Province, China, in 2011–2012. A questionnaire survey was performed among patients with abnormal glucose metabolism aged over 40 years. The frequency of their alcohol intake, the type of alcohol, and the amount of alcohol consumed daily were surveyed. Physical and biochemical examinations were also performed. Then, through the Primary Public Health Service System of Jilin Province, we collected outcomes during the 10‐year follow‐up up to October 1, 2021, including all‐cause mortality, stroke, and CHD. Next, we conducted logistic regression to analyze the relationship between baseline alcohol consumption and 10‐year outcomes, and risk ratio (RR) and 95% CI were calculated by adjusting for different clinical indicators. A A total of 4855 patients with T2DM and prediabetes (35.2% men and 64.8% women) were included in the baseline analysis. Outcomes of 3521 patients during the 10‐year follow‐up were obtained, including 227 deaths, 296 new‐onset strokes and 445 new‐onset CHD. Occasional drinking (less than once a week) was associated with a reduced 10‐year all‐cause mortality, with an RR of 0.511  after adjustment for age, gender, medical history, and lifestyles and an RR of 0.50  in a fully adjusted model including additional biochemical indicators. In addition, heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) was significantly associated with an increased incidence of stroke, with an RR of 2.503  after the adjustment for age, gender, medical history, lifestyles, and biochemical indicators. No significant association was found between alcohol consumption and new‐onset CHD.For patients with abnormal glucose metabolism, occasional drinking (less than once a week) reduces the risk of all‐cause mortality, while heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) significantly increases the risk of new‐onset stroke. They should avoid heavy alcohol intake, but light alcohol consumption or occasional drinking is acceptable. Additionally, it is crucial to control blood glucose and blood pressure and keep performing physical activities. HighlightsThis long‐term longitudinal study demonstrates the association between alcohol consumption and health outcomes in patients with abnormal glucose metabolism including type 2 diabetes mellitus and prediabetes.Occasional drinking (less than once a week) reduces the risk of all‐cause mortality, while heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) significantly increases the risk of new‐onset stroke.Patients with abnormal glucose metabolism should avoid heavy alcohol intake, but light alcohol consumption or occasional drinking is acceptable.This study provided evidence of lifestyle instructions for patients with abnormal glucose metabolism. The prevalence of DM in Chinese adults was 4.5% in urban areas and 1.8% in rural areas in 2002, while it rose to 11.2% in 2015–2017. Furthermore, in 2010, 493.4 million adults  had prediabetes.22.1The baseline survey was a part of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study (REACTION)2.2Patients with (1) acute stress reactions such as infection, trauma, and surgery; (2) pregnancy; and (3) a recent history of fever were excluded from this study. Furthermore, we excluded stroke at baseline when the target outcome was stroke and excluded CHD at baseline when the target outcome was CHD.2.3Basic information, including name, gender, age, medical history, smoking and drinking history, physical activity , and sedentary behaviors, was obtained by trained physicians or public health workers.2.4Height and body weight were measured according to a standard protocol, and body mass index (BMI) was calculated as body weight in kilograms divided by the square of height in meters.2.5After an overnight fast of at least 8 h, the levels of fasting plasma glucose (FPG), 2‐h postprandial plasma glucose (PPG), serum lipid, and glycosylated hemoglobin (HbA1c) were measured, and the hepatic function and renal function were evaluated.2.62.6.1Subjects who smoked at least one cigarette per day or seven cigarettes per week for more than 6 months were defined as “smokers.” Individuals who never smoked or smoked occasionally were defined as “nonsmokers.”2.6.2Alcohol intake was classified into three categories based on frequency: (1) no alcohol consumption, (2) occasional alcohol consumption (less than once a week), and (3) frequent alcohol consumption (at least once a week). Based on the amount of drinking, alcohol consumption was classified into (1) light alcohol consumption (<5 g/day), (2) moderate alcohol consumption (5–29.9 g/day for men and 5–14.9 g/day for women), and (3) heavy alcohol consumption (≥30 g/day for men and 15 g/day for women) .2.7Ideal physical activities were defined as ≥150 min/week at moderate intensity, ≥75 min/week at vigorous intensity, or ≥150 min/week at moderate and vigorous intensity.2.8Sedentariness refers to the state of being sedentary for an average time of ≥30 h per week.2.9We obtained annual physical examination results recorded by physicians in the community in the Primary Public Health Service System of Jilin Province. We assessed the outcomes, including all‐cause mortality, stroke (including ischemic and hemorrhagic stroke), and CHD, and outcomes that occurred after baseline were identified according to the first record in the system.2.10U test and Pearson chi‐square test, respectively. Logistic regression was conducted to analyze the relationship between alcohol consumption at baseline and the risk of 10‐year all‐cause mortality, new‐onset stroke, and CHD. Baseline age, gender, disease history, lifestyles, and biochemical examination results were further adjusted for models. Other baseline risk factors associated with 10‐year outcomes were also analyzed. Risk ratio (RR) and 95% CI were calculated for each outcome. As for the missing values, we used the regression imputation method to replace the missing values for the categorical variables and used the dummy variable method to replace the missing continuous variables. All reported p values were two‐sided, and p < 0.05 was considered statistically significant. SPSS 24.0 was used for statistical analysis, and GraphPad Prism 7.0 was used for forest mapping.Baseline data were grouped by gender. Continuous variables which were abnormally distributed were represented as medians (25th and 75th percentiles), and categorical variables were shown by counts and percentages. Differences between the two groups were analyzed by the Mann–Whitney 33.1The baseline characteristics of subjects are summarized in Table 3.2The 10‐year follow‐up outcomes of the 3521 subjects were obtained from the Primary Public Health Service System of Jilin Province. As shown in Table 3.33.3.1Compared with never drinking, occasional drinking was more significantly associated with a reduced 10‐year all‐cause mortality, with an RR of 0.511  after adjustment for age, gender, disease history, smoking, ideal physical activities, and walking. A significant association was observed in fully adjusted models considering age, gender, disease history, smoking, ideal physical activities, walking, and serum biochemical indicators, with an RR of 0.50  , 2.474 , and 2.503 , respectively (Table .975), 2.p > 0.05).Furthermore, we found no significant association between alcohol consumption and new‐onset CHD , history of hypertension , elevated HbA1c , and creatinine  were associated with all‐cause mortality Figure . Increas4To our knowledge, this is the first long‐term observational study focusing on the association between alcohol consumption and CVD and all‐cause mortality in China. We conducted a 10‐year longitudinal study on Chinese people with abnormal glucose metabolism and suggested the impact of alcohol consumption on health outcomes. We found that compared with never drinking, occasional drinking was more significantly associated with a reduced risk of all‐cause mortality, with an RR of 0.50  in fully adjusted models. Furthermore, compared with light consumption, heavy alcohol consumption was more significantly associated with increased new‐onset stroke . No significant association was found between alcohol consumption and new‐onset CHD. Age, history of hypertension, HbA1c, and creatinine levels were positively associated with all‐cause mortality. Age, history of hypertension and CHD were positively associated with new‐onset stroke. Female gender was associated with increased new‐onset CHD, while moderate‐intensity activities and higher HDL‐C were associated with a lower risk of CHD.On the one hand, we chose the population with glucose metabolism disorders because the guidelines for diabetes provided few instructions on alcohol consumption. Most previous studies have shown that drinking was harmful for individuals with diabetes, and we often instructed them to limit alcohol consumption. On the other hand, the impact of alcohol consumption on health outcomes, especially mortality, stroke, and CHD, was still controversial. In the present longitudinal study, we sought to determine whether alcohol consumption was harmful and how much alcohol consumption was appropriate for people with abnormal glucose metabolism.The ADVANCE studyThe mechanisms of the adverse effects of heavy alcohol consumption on stroke are as follows: Excessive alcohol intake may elevate the level of blood pressure and TG in people with diabetes,The present study has several limitations. First, the follow‐up outcomes were obtained from the service system, and the data might not be accurate. The information on alcohol consumption was self‐reported, and recall bias could exist. Second, we did not take abstainers into consideration. Instead, we calculated the amount of alcohol consumed as long as the subject drank. Third, subjects with T2DM and prediabetes were not analyzed separately, so we could not know whether the association between alcohol consumption and health outcomes was the same in these two cases. In the future, we will expand the population size, collect more information and clinical data, and refine the grouping. Forth, because we acquired the outcomes 10 years after baseline, we could not know the changes in alcohol consumption over time and the baseline variables that could change with time. We will focus on the effect of time on the association and get relatively complete clinical data in future work. In addition, in‐depth studies will be conducted to investigate the essential association between alcohol consumption and CHD, stroke, and other outcomes.5This study demonstrates the association between alcohol consumption and health outcomes of patients with abnormal glucose metabolism in China. Occasional drinking (less than once a week) decreases all‐cause mortality, while heavy alcohol consumption (≥30 g/day for men and ≥15 g/day for women) increases the prevalence of stroke. Heavy alcohol consumption causes CVD, while occasional or light alcohol consumption improves the detrimental outcomes. Patients with abnormal glucose metabolism should avoid heavy alcohol intake, but they should not be prevented from occasional or light alcohol consumption. In addition, it is crucial for them to control blood glucose and blood pressure and keep performing physical activities.Y.L., G.W., and X.G. contributed to the conception and design of the study. Y.G., X.X., G.W., F.L. and Y.L. conducted the baseline investigation of this study. M.C. and F.L. collected the events of the 10‐year follow‐up. Y.G. organized the database. X.X. performed the statistical analysis. M.C. wrote the first draft of the manuscript. X.G. revised the manuscript. F.L. gave diet and exercise introductions to patients with diabetes and prediabetes. All authors contributed to manuscript revision and read and approved the submitted version.This study was funded by the Department of Science and Technology of Jilin Province (China) (20210303001SF and 20170623005TC) and Finance Department of Jilin Province (China) (JLSWSRCZX2021‐075).Mengzhao Cui, Fei Li, Xiaokun Gang, Yuan Gao, Xianchao Xiao, Gang Wang, Yujia Liu, and Guixia Wang declare that they have no conflict of interest.


While the efficacy of immune checkpoint inhibitors (ICIs) reportedly varies among metastatic sites and progression patterns (classified as systemic progression [SP] or mixed progression [MP]), the clinical efficacy of ICIs against gastric cancer remains unclear. The response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer was investigated retrospectively.Seventy‐four advanced gastric cancer patients with measurable lesions who received nivolumab monotherapy between 2015 and 2020 were enrolled. Progression‐free survival (PFS), overall survival, response at each metastatic site, and clinical outcomes according to progression pattern were analyzed retrospectively. SP and MP were defined as progression in more than half of the lesions and progression in half or fewer of the lesions, respectively, in cases evaluated as progressive disease.p < 0.001; liver vs. lymph node, p = 0.03). Patients with MP had superior PFS to those with SP . In MP group, patients with treatment beyond progression (TBP) with nivolumab had a trend of longer post‐progression survival than those without TBP .Thirty‐five (47%) and 27 (36%) patients had SP and MP, respectively, and 12 (16%) patients experienced no progression. The progression rates of target lesions in the lung (44%) and liver (57%) were significantly higher than that in the lymph nodes (18%) (lung vs. lymph node, Patients with MP had a longer PFS than those with SP. Lung and liver metastases had a poorer response to an ICI than lymph node metastases. In advanced gastric cancer treated with nivolumab, patients with mixed progression had a longer progression‐free survival than those with systemic progression. Lung and liver metastases had a poorer response to nivolumab than lymph node metastases. Subsequently, nivolumab combined with chemotherapy as a first‐line treatment has shown favorable survival in the CheckMate 649 trial and the ATTRACTION‐4 trialImmune checkpoint inhibitors (ICIs), such as programmed death‐1 (PD‐1) inhibitors, have shown better clinical outcomes of patients with various malignancies.Recently, some studies have shown different responses to ICIs according to metastatic site,Furthermore, in patients with advanced gastric cancer, a post‐hoc analysis of the ATTRACTION‐2 trial suggested that treatment beyond progression (TBP) with nivolumab might confer a better post‐progression survival (PPS) than a placebo, and the progression patterns were associated with the survival of TBP with nivolumab.In this retrospective study, we investigated the response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer. Additionally, whether the benefit of TBP with nivolumab depends on progression patterns were also investigated.22.1We retrospectively analyzed consecutive advanced gastric cancer patients who received nivolumab monotherapy as a third‐ or later‐line treatment between March 2015 and May 2020 at the National Cancer Center Hospital, Tokyo, Japan. Both doses of nivolumab, 3 mg/kg and 240 mg/body every 2 weeks, were acceptable to the subject. The main selection criteria for this retrospective study were as follows: (a) gastric or esophagogastric junction adenocarcinoma in histology; (b) prior treatment with two or more lines of chemotherapy, including fluoropyrimidine‐ and taxane‐based regimens; (c) an Eastern Cooperative Oncology Group Performance Status of 0–3; (d) measurable disease; and (e) at least one response evaluation based on a computed tomography (CT) scan with a 5‐mm slice thickness completed after starting treatment with nivolumab. This study was approved by the Institutional Review Board of the National Cancer Center . This research was conducted in accordance with the ethical principles set out in the Declaration of Helsinki.2.2Patients were classified into SP or MP according to the definitions described above when target lesions and/or nontarget lesions exhibited progression and/or a new lesion appeared, as determined using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.Overall tumor response was assessed and classified as a complete response (CR), a partial response (PR), stable disease (SD), or PD according to RECIST, version 1.1.p < 0.10 in univariate analysis were considered potentially relevant and were included in the multivariate Cox regression analysis. The statistical analyses were performed using the SPSS software package , SAS version 9.4 (SAS Institute), and R version 4.0.2 software (R Core Team). All tests were two‐sided; p < 0.05 was considered statistically significant.Response rates were compared by the chi‐squared test. PFS, OS, and PPS were estimated using the Kaplan–Meier method and were compared using the log‐rank test. Prognostic factors for PFS and OS were explored using univariate and multivariate analyses with Cox regression models. Prognostic variables showing 33.1n = 35), no assessable CT examination (n = 19), prior use of an ICI as a first‐ or second‐line treatment (n = 9), or a histology other than adenocarcinoma (n = 6). Finally, 74 patients were identified as the subjects of this study. The baseline characteristics of the subjects are shown in Table The subjects were 143 patients with advanced esophagogastric junction and gastric cancer who received nivolumab between March 2015 and May 2020 at the National Cancer Center Hospital. Sixty‐nine patients were excluded because of the absence of a target lesion , with one CR and five PRs, and the disease control rate was 39.2% . The median PFS was 1.8 months , and the 6‐, 12‐, 18‐, and 24‐month PFS rates were 12.5% , 8.9% (3.5%–17.6%), 8.9% (3.5%–17.6%), and 8.9% (3.5%–17.6%), respectively. The median OS was 6.8 months , and the 6‐, 12‐, 18‐ and 24‐month OS rates were 52.0% , 31.3% (19.9%–43.4%), 17.9% (8.2%–30.4%), and 14.9% (6.1%–27.3%), respectively Figure .3.3p < 0.001) and the liver (p = 0.03) than in the lymph nodes  were 20% 13/66), 14% (3/22), 0% (0/16), and 9% (6/68), respectively, while the PD rates were 18% (12/66), 27% (6/22), 44% (7/16), and 57% (39/68), respectively. The PD rate were significantly higher in the lung ; however, the OS did not differ significantly between patients with MP and those with SP   and 27 (36%) patients had SP and MP, respectively, and 12 (16%) patients had no progression. Patient background of SP or MP are shown in Table ) Figure .p = 0.161)   patients received TBP with nivolumab after initial MP. Although the histological type was unequally distributed between the TBP and no TBP groups Table , other c8% patien) Figure . The six) Figure . No resp3.5p < 0.10. Male had a trend of a longer OS  and a diffuse‐type histology , liver metastasis  and peritoneal metastasis  had a trend of a shorter OS. In the multivariate analysis, a diffuse‐type histology , liver metastasis  were associated with a shorter PFS. In addition, a diffuse‐type histology  and liver metastasis  were associated with a shorter OS  infection, microsatellite instability (MSI), and PD‐L1 expression. It has been suggested that EBV infection status in gastric cancer may be a biomarker for ICIs, but this remains unclear.In conclusion, the response to nivolumab varied according to metastatic site, resulting in different progression patterns, and PFS was significantly longer for patients with MP than those with SP. The continuation of nivolumab treatment after MP might be a useful treatment option. Future studies are warranted to investigate the biological mechanisms of the different responses according to metastatic site and biomarkers for selecting candidates for treatment with ICIs beyond progression.Toru Kadono: Conceptualization (lead); data curation (lead); formal analysis ; writing – original draft (lead). Satoru Iwasa: Conceptualization ; data curation ; formal analysis ; validation ; writing – review and editing . Kengo Nagashima: Conceptualization ; formal analysis (lead); validation ; writing – review and editing . Kotoe Oshima: Conceptualization ; validation ; writing – review and editing . Shun Yamamoto: Conceptualization ; validation ; writing – review and editing . Hedekazu Hirano: Conceptualization ; validation ; writing – review and editing . Natsuko Okita: Conceptualization ; validation ; writing – review and editing . Hirokazu Shoji: Conceptualization ; validation ; writing – review and editing . Yoshitaka Honma: Conceptualization ; validation ; writing – review and editing . Atsuo Takashima: Conceptualization ; validation ; writing – review and editing . Ken Kato: Conceptualization ; validation ; writing – review and editing . Toshikazu Ushijima: Conceptualization ; validation ; writing – review and editing . Narikazu Boku: Conceptualization ; validation ; writing – review and editing .This study received no specific grant from any backing agency in the public, marketable, or not‐for‐profit sectors.Author SI has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author KN has received consulting fees from Toray Industries, Inc. and a speaker honorarium from Pfizer R&D Japan G.K. Author SY has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author HH has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author NO has received research grants from Ono Pharmaceutical and Bristol‐Myers Squibb. Author HS has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author YH has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author AT has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author KK has received research grants and a speaker honorarium from Ono Pharmaceutical and Bristol‐Myers Squibb. Author TU has received research grants and a speaker honorarium from Company Ono Pharmaceutical and Bristol‐Myers Squibb. Author NB has received research grants from Ono Pharmaceutical and Takeda Pharmaceutical and a speaker honorarium from Ono Pharmaceutical, Bristol‐Myers Squibb, Taiho Pharmaceutical and Daiichi‐Sankyo. The other authors declare that they have no conflict of interest.This study was approved by the Institutional Review Board of the National Cancer Center, Japan . This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.Patient consent was obtained through an opt‐out method.Appendix.Click here for additional data file.


Extended hospitalization due to coronavirus disease 2019 (COVID‐19) is associated with residual musculoskeletal and functional deficits lasting even 6 months after discharge; therefore, it is crucial that post‐hospitalized patients are promptly assessed. The aim of this study was to identify post‐COVID‐19 patients' functional status and quality of life, as well as to investigate their inter‐relatedness 2–3 weeks after hospital discharge.The study included 39 post‐COVID‐19 patients previously hospitalized in the Clinic for Infectious Diseases at the University Clinical Center of Kosovo (UCCK) from August to December 2021. Physiotherapeutic assessment encompassed socio‐demographic and clinical data including Short Physical Performance Battery (SPPB) for physical functional performance, hand grip strength, 6‐min Walk Test (6MWT) for aerobic capacity and endurance, EuroQol 5‐Dimension 5‐Level (EQ‐5D‐5L) for quality of life, Visual Analogue Scale (VAS) for pain, Borg CR10 for dyspnea, peripheral oxygen saturation and heart rate. Descriptive statistics, Pearson correlation, and multiple linear regression analysis were utilized for data processing.r = 0.719, p < 0.001), grip strength (r = 0.612 p < 0.001), Borg CR10 , 6MWT , and VAS scale . Using the multiple regression analysis, the grip strength, Borg‐CR10, and 6MWT were found to be strongly predictive of SPPB total score.The median (interquartile range [IQR]) for Borg CR10, VAS pain scale, total SPPB, grip strength, and 6MWT were 1 (0–3), 3 (1–6), 9 (8–10), 30.5 (23.2–43.5) kg, 344.5 (312.7–381.7) m respectively, while the mean (SD) for EQ‐5D‐5L index value was 0.7 (0.2). The strongest and most significant correlation was depicted between SPPB total score and its subscales, followed by correlation with EQ‐5D‐5L  conditions, especially in previously hospitalized patients.There are no established core outcome measures to be applied in the framework of physical therapy for post‐COVID‐19 conditions.In our study, post‐COVID‐19 patients had impaired functional status and quality of life, as early as two weeks following hospitalization.We recommend that the Short Physical Performance Battery (SPPB) be used in the future as one of the primary screening tools for post‐COVID‐19 patients following hospitalization. The physiotherapeutic assessment utilized in this study was designed based on Royal Dutch Society for Physical Therapy (KNGF) position statement for COVID‐19.For assessment of pain during the week before evaluation a Visual Analogue Scale (VAS) was used.2) and heart rate (HR) were measured at rest, during, and following the assessment of physical exertion with a portable pulse oximeter .Peripheral oxygen saturation A calibrated hydraulic dynamometer was used to assess the maximum hand grip strength, as an indicator of muscle strength and function. The recommendations of the American Society of Hand Therapists were followed, and the dynamometer was used in the “2” position.2.2.2The 6‐min walk test (6MWT) was used to assess aerobic capacity and endurance. For application of the test guidelines developed by the American Thoracic Society2.2.3Questionnaire EuroQOL‐5 Dimension‐5L (EQ‐5D‐5L)2.2.4p < 0.05 for all analyses.The IBM‐SPSS Statistics 24 software was used to perform the statistical analysis. Demographic and clinical data were presented using descriptive statistics. For categorical variables, frequency analysis was used. The normality of distribution was assessed using the Shapiro–Wilk test. Normally distributed data were presented using the mean and standard deviation (SD), while not normally distributed data with median, as well as 25th and 75th interquartile range (IQR). The Pearson correlation coefficient was used to analyze the relation between the studied variables. The contribution of the tested variables on SPPB and EQ‐5D‐5L was explained using multiple linear regression analysis which covariates were selected based on theoretical considerations and correlation analyses. The confidence level was 95% (0.05), all the tests were two‐sided, and the significance level was set at 33.1In this study participated 39 post‐COVID‐19 subjects, 22 males (56.4%) and 17 females (43.6%). Mean age was 50.15 (12.20). Median duration of hospitalization as a result of COVID‐19 was 10 (7–14) days, whereas the median time frame between subjects' discharge from hospital and physiotherapeutic assessment was 16 (14–18) days. Table 3.22 was 95.8 (1.8), while blood pressure 131.9 (16.2)/86.7 (11.4). Resting perceived exertion or dyspnea measured by Borg CR10 was 1 (0–3), corresponding to very weak dyspnea. Pain intensity assessed using VAS scale was 3 (1–6), which is analogous to light pain. The median for the total SPPB score, which encompasses the scores of all three subscales was 9 (8–10). The maximal possible score for each subscale is 4. The balance ability was found to have the highest score of 4 (4–4), followed by gait speed of 4 (3–4), while the chair stand test showed the lowest score of 1 (1–2). Grip strength was derived from mean value of right and left hands, and the median grip strength was 30.5 (23.2–43.5). In total 30 subjects underwent 6MWT. The remaining nine subjects declared unable or unwilling to do the test. The median walked distance was 344.5 (312.7–381.7). None of the subjects reached their reference 6MWT distance value with a median percentage of covered predicted distance being 54 (47.4–58.6). Subjects showed an impaired health quality of life following hospitalization due to COVID‐19. The mean EQ‐5D‐5L index value was 0.7 (0.2), while on EQ‐VAS scale subjects reported a mean score of 66.8 (16.3). The most common problems were reported with usual activities (74.3%), pain/discomfort (69.2%), and mobility (64.1%), followed by anxiety/depression (23.1%) and self‐care (20.5%). 7.7% of subjects were unable to perform usual activities at all, while 15.4% of them had major problems in performing the same activities. 10.3% of subjects had major problems with mobility, while 7.7% had severe pain/discomfort.Clinical data are presented in Table 3.3r = −0.459, p = 0.003), VAS scale and SPPB balance test , VAS scale and SPPB total score , and VAS scale and EQ‐5D‐5L . Borg CR10 was significantly associated with SPPB gait speed test , SPPB chair stand test , total SPPB score , and EQ‐5D‐5L . Grip strength demonstrated a significant correlation with SPPB balance test , SPPB gait speed test , SPPB chair to stand test , SPPB total score , as well as with EQ‐5D‐5L . A statistically significant relation was also found between SPPB total score and its subscales. SPPB total score was significantly correlated with EQ‐5D‐5L  and 6MWT . 6MWT also showed a significant correlation with the SPPB chair stand test .The results obtained by Pearson's correlation analysis are presented in Table 3.4The multiple regression model for the prediction of SPPB total score included variables VAS pain scale, Borg CR10, grip strength, 6MWT, and EQ‐5D‐5L. After statistically insignificant variables were removed, the model, including grip strength, Borg CR10, and 6MWT explained 64% of the variance in the total SPPB score  m, , it can be conveyed that aerobic STATUS and endurance were generally impaired, given that performance lower than 80% of predicted value is considered diminished.We have found that overall physical performance was shown to be reduced with the median total SPPB score 9 (8–10). Moreover, 67% of patients had SPPB total score <10, while 18% of patients had SPPB total score <7, corresponding to severe physical disability and low function.As an indicator of overall strength,Our results showed that difficulties in endurance and physical performance were accompanied by dyspnea. Patients of our study reported a median Borg score of 1 (0–3), corresponding to very weak dyspnea.Areas of EQ‐5L‐5D that our patients reported most difficulties with were usual activities (74.3%), pain/discomfort (69.2%), and mobility (64.1%). Our results regarding pain/discomfort and mobility are in line with the findings of the systematic review and meta‐analysis of Malik et al.,The correlation analysis showed that SPPB most frequently and significantly correlated with other tested variables. The strongest relation, as expected, was depicted between the total SPPB score and its subscales, followed by a significant correlation with EQ‐5D‐5L. There is a large paucity of literature regarding post‐COVID‐19 patients in terms of relations between different aspects of physical and functional performance, and quality of life. Nevertheless, a strong association between SPPB and EQ‐5D‐5L was reported in other populations with chronic diseases.Using the multiple linear regression analysis, the grip strength, Borg‐CR10, and 6MWT were found to be strongly predictive of SPPB total score, accounting for 64.0% of the total variance. The SPPB has been identified in the regression analysis as the only measure to reflect quality of life. Considering the practicability of SPPB, our results support the previous statements describing it as one of the simple and affordable tools.Our research presents one of the very few scientific studies on post‐COVID‐19 patients describing the level of functional status and quality of life 2–3 weeks following hospital discharge. However, our study has a few limitations. First, the rigorous exclusion criteria in our study contributed to the absence of patients with severe and critical courses of COVID‐19, thus resulting in a relatively homogenous sample size. Considering that none of our patients required the use of a ventilator, nor was admitted to ICU, our findings can be useful for posthospitalized COVID‐19 patients with mild to moderate courses of disease, while an application to other clinical groups or populations should be approached with caution. Second, there was a lack of pre‐hospitalization clinical data of our patients, thus limiting the recognition of the extent of COVID‐19's effect on their functional status and quality of life.5Considering that in our study, post‐COVID‐19 patients had impaired functional status and quality of life, we recommend that all posthospitalized COVID‐19 patients are assessed for physical function, aerobic capacity, endurance and quality of life as early as 2 weeks following hospitalization. Following this prompt assessment, the results allow for early identification of functional impairment and direct the implementation of a patient‐tailored physical therapy program, thus reducing the impact of long‐term sequelae experienced by people with COVID‐19.Based on findings that SPPB most frequently and significantly correlated with other tested variables, as well as that SPPB was predicted by grip strength, Borg‐CR10, and 6MWT, we consider that the SPPB instrument best reflects the functional status of posthospitalized COVID‐19 patients. We recommend that SPPB is used in future as one of the primary screening tools in post‐COVID‐19 patients following hospitalization.Merita Qorolli: Conceptualization; formal analysis; funding acquisition; investigation; methodology; project administration; resources; validation; visualization; writing—original draft; writing—review & editing. Samire Beqaj: Conceptualization; data curation; formal analysis; investigation; methodology; resources; validation; visualization; writing—original draft; writing—review & editing. Dafinë Ibrahimi‐Kaçuri: Conceptualization; data curation; investigation; writing—review & editing. Ardiana Murtezani: Data curation; investigation; resources. Valon Krasniqi: Investigation; resources; writing—review & editing. Amra Mačak Hadžiomerović: Conceptualization; supervision.The authors declare no conflicts of interest.The lead author Samire Beqaj affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.


In addition, the values of TBARS were significantly (p < .05) reduced for treated samples 0.72 mg MDA/Kg in T3 as compared to control 1.17 mg MDA/Kg on the 21st day of storage, whereas a significant increase (p < .05) in TPC from 0.90 mg GAE/g to 3.87 mg GAE/g in T0 to T3 was observed at the start of the study. For TPA, a significant (p < .05) increase was noticed in hardness, chewiness, and gumminess, whereas cohesiveness and springiness showed a non‐significant (p > .05) change in treated samples in relation to control, and the instrumental color (L* and a*) decreased significantly. However, pH, crude fiber, fat, ash, and protein content showed non‐significant (p > .05) variations over time. The sensory evaluation suggested that chicken tender pops supplemented with 6% PPP (T2) presented high overall acceptability and balanced organoleptic properties. Hence, it can be concluded that PPP can be effectively utilized as a natural fiber source, antioxidant, and antimicrobial agent in novel functional foods.Pomegranate peel powder (PPP) is a rich source of many bioactive components particularly polyphenols that are interlinked to various technological and functional properties. In the present study, chicken tender pops were developed with incorporation of PPP, and its effect on quality attributes and storage stability of the product were evaluated. The treatments were formulated using 0%, 3%, 6%, and 9% PPP in replacement of chicken. The physicochemical properties, texture profile, instrumental color, sensory attributes, and storage stability were assessed for 21 days at refrigeration temperature, at a regular interval of 7 days. The results indicated that the inclusion of PPP significantly ( The study evaluated the effects of incorporation of pomegranate peel powder on physiochemical, biochemical, and sensory attributes in development of chicken tender pops in refrigeration storage. Results show that use of pomegranate peel power enhanced antioxidant concentration, antimicrobial properties, sensory characteristics, and improved nutritional profiles while exhibiting potential of natural preservatives. Furthermore, the effect of PPP incorporation on physiochemical characteristics, proximate composition, cooking characteristics, oxidative stability, instrumental color, texture profile, and sensory attributes of chicken tender pops was also assessed to predict the product's storage quality at refrigeration for 21 days.22.1Punica granatum) was procured from the local market of Lahore, Pakistan. The fresh boneless broiler chicken meat was purchased from the local Superstore in Lahore, Pakistan. The meat was packed in small bags of LDPE and held in a refrigerator at 4 ± 2°C for 6 h and later used to develop chicken tender pops.The pomegranate , with few modifications. Briefly, fresh pomegranates were washed thoroughly with distilled water to remove surface dust. The arils were separated from rinds and then cut into medium‐sized pieces. Pomegranate peels (rind) were placed in a tray and dried using a hot‐air oven DOF‐230E  at 50 ± 2°C for 48 hrs. Dried peels were cooled and ground enough to pass through a 20‐mesh sieve to obtain a fine powder with uniform particle size. Pomegranate peel powder was transferred in zipped‐lock high‐density polyethylene bags and stored at room temperature 20 ± 3°C for physicochemical analysis and later used in product development.2.3Proximate analysis  was performed using standard protocols of AOAC . The pH 2.4Treatments of chicken tender pops were prepared using various concentrations of PPP replacing chicken meat. 0%, 3%, 6%, and 9% PPP were added to 80%, 77%, 74%, and 71% boneless meat, respectively, while other ingredients were added according to weight ratio (w/w) mentioned in Table 2.5The pH of chicken tender pops was estimated by the dipping probe of a digital pH meter  in a homogenized sample by following the method of Santhi et al. . The wat2.6Moisture, fat, protein, ash, and crude fiber content of chicken tender pops were determined by following the standard protocols of AOAC, 2.7g for 15 min. Samples were heated at 95°C for 60 min in a water bath, followed by cooling at 25°C. The absorbance of samples was measured at 532 nm through the Tecan Sunrise spectrophotometer (Austria).Folin–Ciocalteu method, as described by Firuzi et al. , was use2.8The instrumental texture profile  of chicken tender pops was evaluated using a Universal TA‐XT plus texture analyzer  and its propriety Exponent software, version V.5.1.1.0, as described by de Paiva et al. . A slice2.9L* (lightness), a* (redness), and b* (yellowness) of samples were measured , coliform count , Staphylococcus , Salmonella , and Listeria monocytogenes . All microbial counts were calculated as logarithms of colony‐forming units per gram (log cfu/g). Staphylococcus, Salmonella, and Listeria analyses were performed at 0 and 21 days of storage, whereas all other investigations were made for the whole storage period at an interval of 7 days  at the Department of Food Sciences, University of the Punjab, Lahore, Pakistan. The items were air fried and served warm for a few minutes before sensory analysis. The samples were evaluated based on their general acceptability, juiciness, flavor, appearance, color, texture, and juiciness. Around 4.30 p.m., sensory evaluation was conducted in a setting with adequate lighting. The panelists offered potable water to rinse their mouths after each sample  were considered statistically significant.Acquired data were articulated as the mean values of three replicates, and standard deviations were analyzed statistically by evaluating variance using SPSS version 25.0. Two‐way ANOVA and LSD's post hoc analysis were used for multiple comparisons. For all tests, p‐values of  decrease was observed in treated samples compared to the control, which could be linked to higher acidity of pomegranate peel powder. During refrigerated storage, pH of all treatments decreased non‐significantly (p > .05), possibly due to growth of lactic acid bacteria or the conversion of glycogen into lactic acid. A similar effect was reported by Rupasinghe et al. (p < .05) improved by the addition of pomegranate peel powder, which is recorded as 43.60%, 46.36%, 47.87%, and 49.36% for T0 (0% PPP), T1 (3% PPP), T2 (6% PPP), and T3 (9% PPP) respectively. Similar results were reported by Akhtar et al.  decreased by the addition of pomegranate peel powder ranging from 60.05 ± 0.03% to 55.08 ± 0.005%, attributed to the replacement of meat with dried peel powder. A considerable drop in moisture content was observed during storage associated with evaporation into surroundings, but this decrease was lower in treated samples, as elucidated in Table The moisture content of chicken tender pops was significantly (3.4p < .05) increased for both control and treated samples throughout refrigerated storage. However, the increase in treated samples was significantly lower than the control sample, as presented in Figure p < .05) reduced the TBARS of meat. However, the TBARS increased during the storage period, a consequence of lipid oxidation in muscle foods.Antioxidants are compounds that exert a free radical scavenging effect and bind them, preventing degenerative diseases  increase was noticed in hardness, chewiness, and gumminess, whereas cohesiveness and springiness showed a non‐significant (p > .05) change in treated samples in relation to control. High concentrations of PPP followed by moisture loss contributed to the increased hardness in treated samples. Conversely, control samples showed low shear force values . Our results are consistent with Sharma and Yadav  affected the color of chicken tender pops during storage. A significant decrease was observed in lightness (L*) of treated samples as compared to control , but it was more significant in the control sample than in treated samples  reduced the yellowness (b*) in treated samples 12.15–12.37 than control 12.83. However, heterogeneous variation was observed for b* throughout the storage as depicted in Figure p > .05) increase was observed. Pereira et al.  for chicken tender pops significantly (p < .05) increased with the advancement of the storage period in all treatments as shown in Figure The effect of PPP supplementation on the microbiological safety of chicken tender pops during storage was investigated through the assessment of total viable count, psychotropic count, and coliform count along with Staphylococcus, Salmonella, and Listeria were investigated as human pathogens at the beginning and the end of the study. The results showed negative values for all of these bacterial pathogens during the entire storage period hence conforming to safety legislation, Regulation EC No 2073/2005  containing different concentrations of pomegranate peel powder at different storage intervals are represented in Figure 3 (9% PPP), darker red color was observed with a slight dryness with the progression of storage. In general, the best sensory scores were received by T2 chicken tender pops containing 6% PPP. Hence, the panelists declared chicken tender pops with 6% pomegranate peel powder (T2) as the best treatment for all organoleptic properties during the study period. The results for sensory evaluation of color and textural properties (juiciness and tenderness) can be correlated with instrumental color analysis and texture profile analysis. Sensory scores for color were decreased as an increase in PPP concentration and results are analogous to L* and a* values which show increased darkness in product due to myoglobin oxidation and PPP color. Furthermore, instrumental texture analysis showed increased hardness and dryness because of moisture loss that will ultimately lower the juiciness and tenderness of the product.Sensory attributes  of prepared treatments (T3.103 (9% PPP), accompanied by coliform count and fat in the control sample at day 0. A slightly lighter color was depicted by T2 (6% PPP) and T3 at Day 0 for TPC and WHC and cooking yield, respectively.A heatmap was generated to analyze all variables pertaining to storage time and pomegranate peel powder concentration Figure . In addi3 for ash, crude fiber, gumminess, and hardness for the whole storage period. On the other hand, neutral color was displayed for moisture in T3 and T0 on days 7 and 14, respectively. Likewise, neutral color was noticed for organoleptic properties  in T0 on day 7. The minimum values in a cluster were indicated by the dark blue color that was spotted in the control sample for all sensory attributes  on the 21st day of storage.Similarly, T0 indicated slight variation for coliform and fat on day 14, whereas T0 showed cooking loss on day 21. The moderate‐color cluster was noted in T3.11A regression analysis was performed to evaluate the correlation among the results of conducted assays on chicken tender pop samples supplemented with pomegranate peel powder shown in Figure b* (yellowness/blueness) value, and cooking loss of sample T3 (6% PPP) at day 7. Cooking yield and WHC revealed comparatively lower values for T1 on day 7. A similar trend was observed for chewiness and gumminess of T2 samples at day 14. Cooking loss and hardness were further reduced for samples T1, T2, and T3 at day 21. Minimum quantities were observed for control sample at day 0.Principal component analysis (PCA) was characterized by reducing a large number of variables to a small number of comprehensive variables, accurately expressing the total amount of data. Signal intensities are used in PCA to highlight the differences between the parameters that were taken into consideration. Figure 4Incorporating pomegranate peel powder reduced the moisture content and significantly improved the product's water‐holding capacity, ultimately enhancing the product's sensory attributes. Furthermore, the inclusion of PPP enhanced crude fiber content in treated samples compared to the control group. Significant elevation in total phenolic content indicated the potential of PPP to be used as a natural antioxidant. In contrast, reduced TBARS elucidated the positive impact of PPP on lipid auto‐oxidation. Hardness, chewiness, and gumminess were considerably affected, whereas springiness and cohesiveness showed minor variations. In addition, PPP retarded pigment oxidation was indicated by retained red color during storage. The reduced microbial load validates the antimicrobial potential of PPP ascribed to the presence of polyphenols and flavonoids. Pomegranate peel powder significantly improves the sensory attributes, but up to a specific limit, as for our study, it was at 6%. Based on our study, it can be concluded that chicken products supplemented with PPP have improved nutritional and sensory profiles and can be naturally preserved for up to 3 weeks at refrigeration temperature.Zunaira Basharat: Conceptualization ; formal analysis ; investigation ; methodology . Maryam Imran: Investigation ; visualization ; writing – review and editing (lead). Naeem Fatima: Investigation (supporting); visualization (supporting); writing – review and editing (supporting). Muhammad Wasim Sajid: Conceptualization ; formal analysis ; investigation ; methodology ; writing – original draft . Muhammad Rizwan Tariq: Conceptualization ; formal analysis ; methodology ; validation . Shinawar Waseem Ali: Conceptualization ; data curation ; investigation ; writing – review and editing . Zujaja Umer: Formal analysis ; investigation ; methodology ; writing – review and editing . Humphrey Garti: Conceptualization ; data curation ; formal analysis ; methodology ; writing – review and editing .We did not receive any funding for this work.The authors have no competing interest to declare.


To identify new trends and potential hotspots in research on rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD).The Web of Science (WOS) database was used to search for RA‐ILD‐related literature published between August 31, 2002 and August 31, 2022. CiteSpace 6.1.R3, VOSviewer version 1.6.17, Scimago Graphica, and Pajek V2.0 visualization software were used to conduct a comprehensive analysis and network visualization mapping of the authors, countries, institutions, journals, cited references, and keywords.Clinical Rheumatology is the journal with the most papers published. Rheumatology was the most cited journal. The citation clusters and keywords concentrated on the mechanism, treatment, and predictive and prognostic factors.A total of 2412 articles were retrieved, and the number of articles published has grown annually since 2002. Eric L. Matteson was the most prolific author, and the Mayo Clinic and UNITED STATES have the highest publishing volume and influence. Pathogenesis, treatment, and predictive and prognostic factors were among the RA‐ILD research directions and hotspots. Antirheumatoid drugs, especially biologics and small molecule inhibitors, were among the most actively researched treatment options. The results of this study provides an in‐depth understanding of the development of RA‐ILD publications, aids researchers in understanding hotspots and trends and provides a new perspective for future RA‐ILD research. Although arthritis is the most frequent RA symptom, extra‐articular symptoms may occur in 50% of the RA population.Researchers have begun to pay more attention to RA‐ILD in view of the above‐mentioned factors. However, some controversies remain regarding RA‐ILD, including pathogenesis, treatment, predictive markers, and prognostic factors.22.1Data were retrieved and collected from the Web of Science Core Collection (WOSCC) database. The search strategy was as follows: (((TS = (rheumatoid arthritis) or TS = (rheumatic arthritis) or TS = (rheumatism arthritis) or TS = (rheumatoid arthritis)) and  or TS =  or TS = (“ILD”) or TS = (pulmonary fibros*) or TS = (pulmonary fibrot*) or TS = (lung fibros*) or TS = (lung fibrot*) or TS =  or TS =  or TS = (pulmonary sarcoid*) or TS = (pulmonary granuloma*) or TS = (lung sarcoid*) or TS = (lung granuloma*))) and LA = (English)) and DT = (Article or Review). The language was English, the literature type was article and review, and the publication date was set from August 31, 2002 to August 31, 2022.2.2Visualization software CiteSpace 6.1.R3, VOSviewer version 1.6.17, Scimago Graphica, and Pajek V2.0 were used for scientometrics analysis. The following information was extracted through the above software: authors, countries, institutions, journals, references, and keywords. Two researchers conducted data extraction to guarantee the reliability and correctness of the research findings. If the two researchers had different findings, they discussed the issue until a conclusion was reached.The use of CiteSpace included: clustering, timeline view, and burst detection analysis of co‐cited references, journal dual map analysis, clustering and burst analysis of keyword detection. VOSviewer was employed for a scientometrics study of authors, nations, and institutions. Specifically, VOSviewer was combined with the Scimago Graphica and Pajek programs to map the global distribution of national contributions and cross‐country cooperation networks, and to show the co‐occurrence analysis of keywords. Figure 33.1We can assess the patterns and rate of research in this field based on the number of publications in each period. The retrieval approach revealed that WOSCC had collected 2412 publications on RA‐ILD (no duplicates were found), with a total of 63,428 citations (self‐citations removed). Each article received an average of 31.12 citations and the H‐index score was 120, which is a crucial measure of a researcher's scientific impact. Since 2022 was not an entire year, the rise only covers the years before 2021, displayed in Figure 3.2The co‐authorship analysis of authors is displayed using the VOSviewer program Figure . Table 13.3The map of the countries that have contributed to RA‐ILD research is depicted in Figure 3.4Based on the literature findings, 590 institutions contributed to this field over the past 20 years. The top 10 most productive institutions, all from the United States, are shown in Figure 3.5Rheumatology (3250).In this study, 2412 articles were analyzed, which were published in 720 different journals. The top 10 active journals published 470 articles on RA‐ILD . The main results showed that the risk factors may be related to age, smoking, anticitrullinated protein antibodies (ACPA), genetic variation, and so forth. Age is a separate risk factor for developing ILD in RA cohorts, with most RA‐ILD diagnoses occurring in the sixth decade of life.The citrullinated protein, also known as ACPA, generates auto‐antibodies. In studies, higher ACPA titers were associated with higher prevalence of ILD, even after adjusting for confounders, including RA and smoking.On the genetic front, the major finding was the MUC5B mutation. A substantial genetic risk factor for the onset of IPF has been identified as the MUC5B promoter variation.There was also an elevated chance of developing RA‐ILD due to other variables, such as certain human leukocyte antigen (HLA) alleles and blood biomarkers. Several HLA variations may be brought on by RA‐ILD, including HLA‐B54, HLA‐DQB1*0601, HLA‐B40, and HLA‐DR4.4.2So far, therapy recommendations for RA‐ILD have mostly been based on trial data from IPF or other CTD‐linked ILDs, like systemic sclerosis‐associated ILD (SSc‐ILD). Meanwhile, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) urged a multidisciplinary approach.The antirheumatic drug therapy for RA consists of both conventional and biologic disease‐modifying antirheumatic drugs (cDMARDs) (bDMARDs). However, drug‐related pulmonary illness, including lung infection, nodules, and ILD, has been associated with cDMARDs and bDMARDs.In patients with RA, methotrexate (MTX) was associated with the development or exacerbation of ILD.Most conventional antitumor necrosis factor (TNF) medications have been documented to cause ILD, including infliximab, etanercept, adalimumab, golimumab, certolizumab pegol, and the IL‐6 receptor (IL‐6R) antagonist tocilizumab.Through the keywords burstiness, we can see that jak inhibitors have been the focus of attention at the forefront of treatment in recent years. According to in vitro research, JAK2 is a crucial intermediary molecule in TGF‐mediated myofibroblast trans‐differentiation, proliferation, and extracellular matrix protein synthesis. The regulating function of JAK2 in the etiology of pulmonary fibrosis was further demonstrated by inhibiting bleomycin‐induced mice pulmonary fibrosis with the JAK2‐selective pharmacological inhibitor CEP3377.4.3Those with RA‐ILD had a 2–10 times higher risk of mortality than those with non‐ILD RA, regardless of the length of the follow‐up period. It is evident that ILD is a serious complication for patients with RA, and its mortality rate is significantly higher than that of patients with RA without ILD.Age, male sex, and history of smoking are all risk factors for RA‐ILD. Furthermore, high‐titer rheumatoid factors (RF) and ACPA have been identified as ILD diagnostic biomarkers.5This is, to the best of our knowledge, the first study to conduct a comprehensive scientometrics analysis of nearly two decades of global RA‐ILD publications. Citations for RA‐ILD research are increasing on an annual basis. We used an information visualization tool to describe RA‐ILD research progress, hotspots, and frontiers over the previous 20 years. These findings can guide RA‐ILD investigation and assist interested researchers in locating potential collaborators. We identified influential authors, institutions, and representative literature in this field. The pathogenesis, treatment, and prediction and prognosis of RA‐ILD are the research directions of RA‐ILD. The similarity research with IPF is direction with respect to the pathogenesis and treatment; antirheumatoid drugs, particularly biological agents and small molecule inhibitors, are prominent therapeutic research directions. Continuous exploration of disease prediction and prognostic factors is critical for improving patient survival rates.Conception and design of the research: Yue Yang and Xieyu Zhang. Acquisition of data: Zixuan Zhang and Xieyu Zhang. Analysis and interpretation of the data: Zixuan Zhang, Kai Zhi, and Jiahe Zhao. Statistical analysis: Xieyu Zhang, Kai Zhi, Jiahe Zhao. Obtaining financing: Wei Cao. Writing of the manuscript: Yue Yang, Zixuan Zhang, Xinwen Zhang. Critical revision of the manuscript for intellectual content: Wei Cao and Xieyu Zhang. All authors read and approved the final draft.The authors declare no conflict of interest.Supporting information.Click here for additional data file.