Background and Objectives: In the last decades there has been an increasing body of research identifying the positive correlation between diabetes mellitus (DM) and solid malignancies, moreover, having shown DM as an independent risk factor for colorectal cancer (CRC). The aim of the present study was to assess the impact of DM on metastatic CRC (mCRC), and to identify possible predictive factors in the successful treatment of mCRC. Materials and Methods: 468 patients with mCRC were included in this retrospective, observational study. A total of 8669 oncological treatment cycles related to 988 distinct chemotherapy lines were analyzed. Data regarding lines of treatment and blood panel values were obtained from the Oncohelp Hospital database. Results: The presence of DM in male patients >70 years was a negative predictor (RR = 1.66 and a p = 0.05). DM seemed to have a detrimental effect in patients whose treatment included bevacizumab . Analysis of treatments including bevacizumab based on DM status revealed lower values of mean TTF in DM+ female patients versus DM-. It was also observed that DM+ patients had a higher mean TTF when undergoing anti-EGFR  therapy . Conclusions: The favorable predictive factors identified were the inclusion of antiangiogenic agents, a higher hemoglobin value, a higher lymphocyte count, the inclusion of anti-EGFR treatment for DM+ patients, a higher creatinine, and a higher lymphocyte count in treatment lines that included anti-EGFR treatment. Unfavorable predictive factors were represented by the presence of DM in female patients undergoing antiangiogenic treatment, neutropenia in male patients, the association of oxaliplatin and antiangiogenic agents, and a higher monocyte count in the aforementioned treatment lines. Colorectal cancer (CRC) remains among the most frequent malignancies throughout the world. In terms of mortality, it stands in the second position, while in terms of incidence it occupies the third . In 2020CRC has been recognized as a marker of the level of social and economic development of a country, with research suggesting a substantial increase in CRC incidence and mortality is to be observed in nations with a medium or high human development index (HDI), due to the adherence to a western dietary pattern and lifestyle . It has There is a growing body of research underlining the importance of dietary and lifestyle variables influencing the risk of colorectal cancer. Physical activity appears to have a protective effect, according to multiple studies. A higher frequency of red and processed meat consumption, as well as alcohol intake, increase the risk of developing CRC . The effA steady increase in new cases globally is also seen in Diabetes Mellitus (DM), according to the 2021 Diabetes Atlas elaborated by the International Diabetes Federation (IDF), with roughly 537 million adults aged between 20 and 79 years old diagnosed worldwide, this number being expected to increase to more than 630 million individuals by the year 2030 .As early as 1910, studies have been conducted in an attempt to find a positive correlation between cancer in all its forms and DM. However, while some studies such as the one led by Doering et al. reported a positive correlation, others like the one led by Stevenson et al. in 1921 showed that no correlation was to be found. In conclusion, studies have failed to unequivocally prove that diabetes is a predisposing factor for cancer, as stated in “Diabetes and Cancer”, written by Elliott P.During the last decades, research has found, through numerous published studies and meta-analyses, that there is a positive correlation between diabetes and some solid malignancies such as hepatocarcinoma and renal cell cancer ,10. WorlAccording to Ana Silva et al., obesity is likely to have a negative impact on CRC outcomes, particularly in male patients . The tumA key determinant involved in both the onset of type II diabetes, as well as in CRC is represented by the insulin/insulin-like growth factor (IGF) system, a multifactorial signaling system that controls energy consumption, cell development, and cancer. Thus far, two insulin receptor (IR) isoforms have been identified, having distinct biological functions. IR-A primarily exerts mitogenic effects, while IR-B exerts influence on cell metabolism. The various ligand-binding abilities of the isoforms, as well as their variable tissue distribution, support this idea. IR-A is more commonly found in fetal and cancerous tissues, whereas IR-B is more commonly found in muscle, liver, and adipose tissue . As repoThe association between DM and CRC is of particular interest, on one hand, given the prevalence of DM in the Romanian population. According to the PREDATORR study, between 1.5 and 1.9 million Romanians have DM, with the prevalence of the disease being 11.6%. Of this percentage, 2.4% were previously undiagnosed. It was observed that the prevalence of DM was higher in men than in women and increased with the advancement in age. Prediabetes, however, was found to be more prevalent (16.5%) in female patients aged between 60 and 79 .On the other hand, CRC trends in Romania show a rate of hospitalization steadily increasing between 2016 and 2018, with a mortality of 34.13/100,000 in the Central and Northern regions of the country, nearly twice as high as the average range in Europe. More recent data from Globocan has estimated the new cases of CRC at 12,938 in 2020 [The study aimed to verify the impact of DM on mCRC patients and to identify predictive factors relevant to the success of mCRC treatment.The present study is an observational, retrospective one, having been led in accord with the Declaration of Helsinki, approval of the Ethical Committee within the Oncohelp Medical Center being granted for the study protocol.Upon searching within the Oncohelp Medical Center patient database, 1069 individual cases of colorectal cancer were identified, based on ICD-10 medical diagnosis codes from C18 to C20. Admissions of said patients to the Oncohelp Medical Center took place between 15 June 2018 and 21 January 2022. All patients included underwent at least one cycle of chemotherapy. Chemotherapy lines initiated before 18 September 2018 were excluded from the study. Of the total number of patients, 468 cases of metastatic colorectal cancer were identified, of which 55.55% (260/478) were in male patients. The database included 8669 oncological treatment cycles related to 988 distinct chemotherapy lines. For each treatment line, the following were documented: last administration date, continuation, or completion of the line after the cut-off date (21 January 2022).A database was created, in which anthropometric data ), diagnoses , hematological and biochemical determinations performed at initiation of each treatment cycle were included.Data was collected and analyzed using SPSS v. 27 statistical software package .Kolmogorov-Smirnov Normality Test was performed in order to evaluate the distribution of variables. The variables with a normal distribution are presented as mean ± standard deviation, while the non-parametric variables are presented as median . For assessing the significance of the differences between groups, we performed the t-Student test for variables with a normal distribution and the Mann-Whitney test for non-parametric variables. Time to treatment failure (TTF) was calculated as the difference between the date of the first and last administration of a treatment line (for a patient with a single administration within a single line).For evaluating the involvement of more confounding factors  in a time-related risk for each palliative treatment line for mCRC (time to treatment failure), we built Cox proportional-hazards models using Cox Proportional Hazards Survival Regression (CPHSR).p-value of <0.05 was considered the threshold for statistical significance.The results were presented as risk ratios and significance levels. A Out of 988 oncology lines, 44.12% (436/988) were administered to female patients and 55.88% (552/988) to male patients. Patients’ ages ranged from 21 to 88 years. The fact that a higher percentage of treatment lines can be observed in the male gender is primarily a consequence of those cases belonging to the 60+ age group. Within the male gender subgroup, two patients were under the age of 30. By age group, the highest prevalence of diabetes was found in men in their seventh decade of life (22%), with women reaching a similar prevalence in their eighth decade (21.3%). The distribution of patients according to gender and age groups is detailed in Regarding the treatment options that were used, of the 988 treatment lines 84.41% (834/988) included fluoropyrimidines, 45.44% (449/988) oxaliplatin, 28.95% (286/988) irinotecan, 3.34% (33/988) trifluridine + tipiracil, 37.14% (367/988) angiogenic treatment and 20.24% (200/988) anti EGFR treatment.p = 0.12). In the same age segment, considering only the treatment lines of the male participants, an RR of 0.74 with a p-value of 0.07 was identified. The presence of DM in male patients over 70 years of age was found to be a negative predictor with a RR = 1.66 and a p-value of 0.05.In the CPHSR analysis, the presence of DM was not found to be a significant negative predictive factor for TTF. Also, no statistically significant results were obtained after evaluating DM presence as a risk factor for TTF by age-groups analysis. However, in patients included in the age group 60–69, there was a favorable predictive effect regarding the presence of DM and TTF (RR (risk ratio) = 0.81, Insulin treatment was present in 9.03% (14/155) of the therapy lines within the group of patients with DM and did not reach statistical significance neither as a risk nor a protective factor.Regarding treatment with fluoropyrimidines (capecitabine and 5-fluorouracil), the maximum mean TTF was 150 days for patients with DM between 70 and 79 years of age, exceeding the maximum TFF of 132 days in patients without DM in their eighth decade of life. Furthermore, the FTT of individuals with DM indicated a clear downward trend for the age group 80 and above, a trend that was not observed in patients without DM .p being 0.14) and a bell curve reaching a maximum in the seventh decade in people who suffered from diabetes. The average TTF was higher in patients with DM for the seventh decade, but statistical significance was not reached . In contrast, for patients with diabetes, the value of TTF seems to decrease with age, at least after the age of 60 .In treatment lines including irinotecan, in the subgroup of patients without DM , the durp = 0.22, possibly due to the reduced number of treatment lines—only 44). At the same time, for patients without DM, TTF averages revealed a similarity in all age groups, with the exception of the outer segments represented by a low number of cases  revealed a similar age-related aspect for patients without diabetes and a bell-shaped curve for patients with DM, without indicating statistically significant correlations by age .t-test . Aside from the previous finding, it was also observed that those individuals with DM had a higher mean TTF when undergoing anti-EGFR therapy . . p = 0.009)  .p = 0.0005) when the whole group of patients was analyzed (916 treatment lines with available lab tests). For the treatment lines administered to DM+ patients, the protective effect was even more marked   .p < 0.001) (p= 0.005). Subsequent tests further confirmed the negative predictive effect of DM+ in female patients treated with bevacizumab: RR = 2.57, p = 0.0001) upon CPHSR verification. The same analysis applied to men did not prove a similar impact .The gender distribution of mean TTF values for treatments including bevacizumab did not reveal significant differences , but add< 0.001) . CPHSR tn = 367), the combination with oxaliplatin resulted in a higher risk for those belonging to the group , in contrast to the combination with irinotecan .Interestingly, among the lines containing bevacizumab . Considering all 200 treatment lines that included anti-EGFR medication, the presence of irinotecan was considered a favorable predictive factor (RR = 0.76 with p = 0.15).Among the 200 treatment lines that included anti-EGFR medication, DM+ was a favorable predictive factor , a reduced progression-free survival median, as well as a shorter overall survival in mCRC patients that had DM .67.7% of patients without DM and 68.3% of patients with DM underwent treatment with oxaliplatin, which is surprising, given the increased risk of developing neuropathy of patients with diabetes mellitus. Furthermore, there are studies showing that hyperglycemia can negatively influence outcomes in patients with stage III CRC, leading to oxaliplatin resistance , invitinRegarding treatment with irinotecan, only 46.1% of patients with DM and 55.5% of those with DM had this agent included in their chemotherapy protocol. Taking into account the more favorable profile given by the addition of irinotecan to the anti-EGFR treatment in patients with DM, and the increased risk posed by the association of antiangiogenic treatment with oxaliplatin, it is worth investigating whether the use of irinotecan could be extended.Patients with DM who received bevacizumab treatment were more likely to have comorbidities than those without DM, being in need of closer monitoring for adverse effects. Despite this factor, the OS was similar between patients with DM and those without, indicating that bevacizumab should not be excluded solely based on DM presence .Regarding data provided by the complete blood panel, anemia was identified as an unfavorable predictive factor for the length of treatment of the entire lot, as well as for the sub-group of patients treated with antiangiogenic agents. These findings are in accord with data found in literature, a study published in Nature by M. Tampellini et al. underlining the utmost importance of maintaining hemoglobin values in the normal range in order for patients to benefit the most from first-line chemotherapy regimens, while anemia has been identified as a strong predictor of inferior response and survival rates in patients with advanced or metastatic colorectal cancer undergoing their first chemotherapy treatment line .Among the unforeseen effects observed in the present study are the favorable impact of a higher lymphocyte count in female patients, as well as the unfavorable effect of a higher monocyte count in antiangiogenic treatment lines. In male patients, though, a higher neutrophil count had a negative predictive quality for the TTF. Similarly, other authors have found that a higher neutrophils/lymphocytes ratio (NLR) represented a negative predictive factor for PFS and OS in metastatic colorectal cancer in patients who were treated with bevacizumab and chemotherapy as a first line .p = 0.07363 and p = 0.06219, respectively).DM was found to be a negative predictive factor in patients undergoing treatment with antiangiogenic agents, while in those patients treated with anti-EGFR, DM was a positive predictive factor, though without reaching statistical significance , a higher hemoglobin value , a higher lymphocyte count , the inclusion of anti EGFR treatment for patients with DM, a higher creatinine value , and a higher lymphocyte count in treatment lines that included anti EGFR treatment.Unfavorable predictive factors were represented by the presence of DM in female patients undergoing antiangiogenic treatment, neutrophilia in male patients, the association of oxaliplatin to treatment lines containing antiangiogenic agents, and a higher monocyte count in the aforementioned treatment lines.


High tumor-infiltrating lymphocyte (TIL) levels are associated with an increased response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). The seasonal fluctuation of TILs in breast cancer is poorly documented. In this study, we compared pre- and post-treatment immune infiltration, the treatment response as assessed by means of pathological complete response (pCR) rates, and survival according to the seasonality of BC diagnoses in a clinical cohort of patients treated with NAC. We found no association between seasonality and baseline TIL levels or pCR rates. We found that post-NAC stromal lymphocyte infiltration was lower when cancer was diagnosed in the summer, especially in the subgroup of patients with TNBC. Our data do not support the hypothesis that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC.Breast cancer (BC) is the most common cancer in women worldwide. Neoadjuvant chemotherapy (NAC) makes it possible to monitor in vivo response to treatment. Several studies have investigated the impact of the seasons on the incidence and detection of BC, on tumor composition, and on the prognosis of BC. However, no evidence is available on their association with immune infiltration and the response to treatment. The objective of this study was to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival (RFS) or overall survival (OS) according to the seasonality of BC diagnoses in a clinical cohort of patients treated with neoadjuvant chemotherapy. Out of 1199 patients, the repartition of the season at BC diagnosis showed that 27.2% were diagnosed in fall, 25.4% in winter, 24% in spring, and 23.4% in summer. Baseline patient and tumor characteristics, including notable pre-NAC TIL levels, were not significantly different in terms of the season of BC diagnosis. Similarly, the pCR rates were not different. No association for oncological outcome was identified. Our data do not support the idea that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC. Breast cancer (BC) remains the commonest and most deadly cancer in women worldwide . In 2020HER2-positive breast carcinomas [Over the past decade, tumor-infiltrating lymphocytes (TILs) have been extensively studied in BC ,9,10,11.rcinomas ,13,14,15Both intrinsic (spontaneous mutations) and extrinsic factors can impart cancer risk through the accumulation of DNA errors. Intrinsic risk factors contribute modestly <10~30%) to cancer development. While several extrinsic risk factors have been identified for different cancers, no single one can account for their risk proportions, suggesting complex mechanisms for their etiologies. These factors include factors related to the characteristics of the host  ,18,19,20% to cancIn oncology, seasonality is a topic that has raised little interest to date. Several studies have reported seasonal variations in the detection of BC, with an increased frequency of tumor detection in fall and winter ,47. ConvThe current study aimed to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival and overall survival according to seasonality in a clinical cohort of patients treated with neoadjuvant chemotherapy.The analysis was performed on 1199 patients with invasive local or locally advanced breast cancer (stage T1–T3NxM0) treated with NAC at the Institut Curie, Paris, between January 2002 and April 2012. The cohort included unifocal, unilateral, and primary tumors, excluding T4 or metastatic tumors. All patients were treated with NAC, and additional treatments were decided in accordance with national guidelines. Four to six weeks following the conclusion of treatment, surgery was undertaken. The examination of retrospective data was approved by the Breast Cancer Study Group of the Institut Curie . The study of tissue specimens and patients was carried out following institutional and ethical guidelines. Patient written informed consent was not necessary under French rules.Two pathologists with expertise in cancer pathology examined the tumor samples . Prior to therapy, a core needle biopsy (CNB) was used to confirm the pathological diagnosis. Cases were designated ER- or PR-negative according to French national criteria if less than 10% of tumor cells expressed ER/PR . ImmunohTumor-infiltrating lymphocytes (TIL) levels were assessed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from pretreatment core needle biopsies and the corresponding post-NAC surgical specimens, following the recommendations of the international TILs Working Group, before  and afteWe defined pathological complete response (pCR) as the absence of invasive residual tumors from both the breast and axillary nodes (ypT0/is N0) after neoadjuvant chemotherapy .The date of breast cancer diagnosis was defined as the date of the first core biopsy with cancer. If the biopsy date was not available, the date of the first physical examination and then the date of the first breast imaging were used. In addition, the dates of the breast cancer diagnoses were grouped into four seasons following a methodology described previously : spring The period from surgery to death, locoregional recurrence, or distant recurrence, whichever came first, was described as the relapse-free survival (RFS). Distant recurrence-free survival (DRFS) was defined as the time from operation to the first distant recurrence or death, while overall survival (OS) was defined as the time from surgery to death. Patients that did not show any of these occurrences documented were censored at the last known contact date. The survival analysis cut-off date was 1 February 2019.p-values lower than 0.05 were deemed significant). For groups of less than 30 patients and variables with multimodal distributions, Wilcoxon–Mann–Whitney tests were used to compare continuous variables across groups. In all other situations, Student’s t-test was utilized. The Kaplan–Meier approach was used to estimate survival probability, and log-rank tests were used to compare survival curves. The Cox proportional hazards model was used to determine hazard ratios and associated 95 percent confidence intervals. In the univariate analysis, variables with a p-value for the likelihood ratio test of 0.05 or below were chosen for inclusion in the multivariate analysis. The final multivariate model was built using a forward stepwise selection approach with a significance criterion of 5%. R software version 4.0.3  was used to process data and perform statistical analyses.For qualitative variables, the study population was expressed in terms of frequencies, whereas medians and corresponding ranges were used for quantitative variables. For each variable, Chi-squared tests were used to explore differences between subgroups (HER2-positive BC. The median age was 48.6 years (range: 23.6–79.5). Most of the patients were premenopausal  and had a normal BMI . For 69.7% of the tumors, the diagnosis was made at the T2 stage (n = 62), mostly with baseline axillary node involvement .One thousand one hundred ninety-nine patients were treated with NAC and included in our cohort . The datp = 0.39; IT TIL levels, p = 0.19)  and last (2012) years of recruitment were collected. There was a progressive increase in patients treated with neoadjuvant chemotherapy from 2003 to 2011. Significant seasonal variations were found in the diagnosis of breast cancer. The number of cases tended to peak in the cold seasons , except for the years 2006 and 2007 . Patient = 0.19) .p = 0.87), as was the case for each BC subtype . Post-NAC str TILs levels were significantly lower in patients diagnosed with BC during the summer and spring compared to patients diagnosed in the winter . After performing a subgroup analysis of breast cancer subtypes, seasonal variation and month of diagnosis were found to be statistically significant only in TNBC   . Tumors p = 0.06 for RFS). Therefore, a univariate cox analysis was performed for the luminal BC group. Patients with luminal BC diagnosed in winter had worse prognoses than those diagnosed in summer , p = 0.01).Seasonality of BC diagnoses was not significantly associated with RFS, DRFS, or OS in the whole population . HoweverIn this study analyzing immune infiltration, response to treatment, and oncologic outcomes according to the seasonality of BC diagnosis in a cohort of patients treated with NAC, we found little, if any, association between seasonality and the parameters we analyzed. Our study adds insights to the existing evidence, summarized in First, in our cohort, the season of diagnosis was evenly distributed throughout the year. In contrast, out of 2,921,714 BC cases diagnosed worldwide, Oh and colleagues [lleagues  found thlleagues  found thlleagues . Seasonalleagues . The autlleagues .Second, we did not find any differences regarding any of the tumor characteristics at diagnosis or in the baseline immune infiltration, and this finding was true also for the subgroup analysis subset by BC subtype. This finding is interesting because it has been suggested that social factors potentially modifying the utilization patterns of healthcare programs, such as holidays, religious events, or the organization of health care, can notably modify tumor size or clinical presentation at diagnosis. Out of 905 patients diagnosed with BC, Paradiso et al. found that tumor size and nodal involvement did not differ in the different seasons of the year. In this study, ER and PR showed significant periodicities, with peaks in January/April and in July, respectively [ectively . Though ectively ,51. Studectively . Regardiectively , but we Third, response to NAC was not modified by seasonality. To our knowledge, we report data on response to chemotherapy for the first time. Such a negative association can be explained by either: (i) a genuine absence of effect or (ii) a lack of power below the level needed to detect a slight effect. It would be of interested for other studies to investigate whether seasonality impacts the response to chemotherapy or to the immunotherapies that are becoming cornerstones of other cancer localizations, such as lung cancer and melanoma.Fourth, in our cohort, post-NAC stromal TILs were lower when the BC was diagnosed in summer compared to the other seasons. Our team previously showed that post-NAC TILs are very low and mainly driven by response to treatment [reatment  and by tFifth, we did not find any association with oncologic outcomes. The literature on the impact of seasonality on mortality shows discordant findings. Several small-sized studies found a positive prognostic impact from BC diagnosis in the summer [e summer ,54,62,63e summer ,65, while summer . For theOverall, our study fills a gap in the existing literature on seasonality by describing the first cohort including BC patients treated with NAC. The study limitations include constraints on the research design and methodology, as well as the low efficacy, potentially leading to a lack of statistical power. Findings from one country or a given health care system may not be generalizable to other countries and sociological settings. The role of seasonality in natural history is complex and multifactorial, and we cannot exclude the possibility that a larger number of patients together with more detailed sociodemographic, clinical, and biological parameters could have unmasked significant associations. It was not possible to assess the physiological levels of vitamin D or melatonin as proxies for interannual and inter-regional variations in sunshine hours, temperature, and rainfall and the limited but existing changes in climate throughout Metropolitan France. Finally, we did not perform immunophenotyping to correct the differentiation in the tumor immune profiling. Recent data suggest that, while high TIL infiltration is associated with better outcomes, in ER-positive breast cancer patients, only immune infiltrates expressing PD-1+ and exhausted CD8+ T cells can predict the response to immune checkpoint inhibitors . However


The substitutability of energy and non-energy factors is the key issue in framing and planning energy policies. Therefore, we determine a translog production function for the transport sector, including inputs labor, capital and energy. The research analyzes factor output and substitution possibilities from 1990 to 2019. Outcomes show (a) labor output elasticity is higher, followed by energy and capital. (b) All the substituting factors are rising return to scale, with relatively high substitution  between capital-labor, capital-energy and labor-energy, which proposes that the substitution between capital-labor and capital-energy could be attained through updating technology. Therefore, by giving maximum capital to the transport sector, appropriate energy-conserving technology could be maximally encouraged, and capital-energy substitutability would have better results in the future. (c) Though, technical progress is calculated to be between 0.009 and 0.14 between the various inputs. The input labor-energy is quicker substitutes with their relative difference in technological progress, while capital also presents proof of convergence. By assigning additional capital to the transport sector, energy-saving technologies could be enhanced and CO2 emissions reduction could be achieved. Finally, advancement in capital and skilled labor and, thus, substitution between energy-labor and the transition of labor-capital can be achieved.The transport sector is a key engine of Bangladesh’s quick oil demand growth. It accounted for 64.4% of overall Bangladesh oil consumption in 2019 and is, therefore, a third contributor to CO It has become one of the large energy-consuming sectors that consider energy conservation and global warming because of its large dependence on oil and inadequate reliable substitutive fuels [2es will rise by almost 50% by 2030 and by over 80% by 2050. The rapid expansion of road vehicles, especially private vehicles, has ensured in rising of the overall oil energy consumption by 2638.60 million tons of oil equivalent (Mtoe) in 2019 [2es. Thus, the road sector leads the CO2es by 11.9% by road transport, aviation by 1.9%, and shipping by 1.7%, 4.3% by navigations, rail by 1.8%, and rail by 0.4% and pipelines by 0.3% [The transport sector is imperative in a market-oriented economy and plays an important role in influencing income scale worldwide . Althougve fuels . The trave fuels . As per ve fuels , global Geographically, Bangladesh has numerous opportunities, such as delta plain, predominately forest, coastal line of 710 km, airline routes, ports, and roads for export and import with bordering countries  proposing the most cost-effective and productive transit ways. These lines link central Asian countries and give a feasible and economical route to neighboring countries, such as China, Pakistan, Iran, and Afghanistan. Thus, regional and international transport networking with Bangladesh and other communication system enhancement is necessary. As per the Bangladesh Bureau of Statistics [2es lessening target below 24% by 2030 [The total road length in Bangladesh is 22,418.95 km as of the year 2020 [2 emitting sector after power and industries [2es are challenging for emerging nations like Bangladesh, for example in China, the transportation sector has proven by employing social and environmental targets in reducing pollution, accidents, and road destruction [The transport sector, the third-largest COdustries , has imptruction ,12.2es from Bangladesh’s transport sector. 2es on the global scale in 2019 and has been the second biggest carbon emission source [2-emitting countries of the world were China, US, India, Japan, Iran, South Korea, Canada, and Saudi Arabia, respectively, whose pollution emissions added to the world two-thirds [2es. This is because different countries built policies under technological development and fuel substitution to declining fossil fuel consumption to minimize their share of global emissions [2es. To attain this goal, the Bangladesh government should make more efforts  to concentrate on energy substitution and CO2 reduction.In the context of scientific research, the transport sector is an engine of economic and social development, created 8222 Mt COn source . Though,o-thirds . In 2018missions ,72. For missions  and Razamissions  examinedmissions  and Inte2es lessening in Bangladesh, which is in line with Raza and Hassan [2es and natural gas consumption in Bangladesh’s various sectors  and non-energy  factors for Bangladesh’s transport sector to give policy suggestions and figure out real transport structures for the present and future. According to study objectives, the current study examines the degree to which energy and non-energy inputs are useful and could be substituted to guarantee policies to get maximum economic growth with pollution reduction, and energy security. According to Christensen et al. [2es, but the current study is based on updated statistics and include all kinds of transportation  in Bangladesh and transport CO2es policies linked to NDC [The motivation and innovation of this study are as follows: first, as per the energy and non-energy factors, it is necessary to analyze the effectual output of the transport sector of Bangladesh. The factors and their substitution are important for transport planning, energy consumption, technical progress, and COd Hassan . Concernnstance, ,25,59,67n et al. , the tran et al. , and (e)n et al.  is emplon et al. . But, thn et al. . FinallyFurther part of the current study is organized as: section 2During the last two decades, Bangladesh’s transport sector has been one of the highest-priority investment sectors for the Government and related agencies . During Among the various transport sources, road transport is taken to the fortitude of Bangladesh transport. As per the Bangladesh Economic Review , various2es from the transport sector of Bangladesh.As transportation, especially the road sector is the very astounding contributor to ecological variation in Bangladesh. As per The World Bank  report, 2-emitting sector after the industrial sector, Bangladesh can play an imperative part in this background. The elasticity of substitution between energy and non-energy factor inputs is seriously imperative for energy policy in various sectors, analysis and planning. The implication of energy-conserving technologies in terms of production operation might be described by the substitutability of capital for energy [2es and labor-intensive for maximum output. It is, therefore, the substitutability between labor, capital and energy consumption imperative to energy policy from a future perspective. The key objectives explore to see the transport energy, and CO2es and provide policies to attain maximum economic growth, energy substitutability and natural maintainability.Regarding the chances and challenges, present output and future viewpoint for transportation expansion; Bangladesh transport acquires worldwide values from the outlook for efficiency, atmosphere and energy conservation. Bangladesh has signed two World Bank-supported projects to support lessening energy deficiency and encourage the transport division, such as the Air Quality Management Project (AQMP) and Learning and Innovation Loan (LIL). The objective of these projects is to develop and implement actions that were multi-sectorial, and that presented how to widely report air quality and urban transport issues . From thr energy . Analyzir energy ,17. Sinc2es reduction in Bangladesh’s transport sector in the current scenarios from 2017 to 2019?, and (iv) in the scientific and societal community, what is the relative difference in the technological progress of energy and non-energy factors during the analyzed during 1990–2019? Thus, to achieve future demand and supply, the government should focus on energy, non-energy, inter-factor, and inter-fuel substitution levels. In specific, the results of future forecasts for energy needs are consistent when the demand models consider substitution elasticity [2es and provide policy suggestions to obtain high economic growth, energy substitution, and natural maintainability.Since energy is one of the key production factors, energy and non-energy inputs are set into production as per a certain portion and can substitute for one another to certain level. Under the principle of substitutability, it is probable to achieve the dual goals of economic progress and energy conservation by shifting the combination of energy and non-energy inputs. Hence, there are four main points that should analyze in the transport sector. (i) To what extent can other inputs substitute for energy, for example, fossil fuels to renewable energy or low-carbon emitting fuels?; (ii) what are the impacts of substitutability outcomes on the transport sector’s development and energy conservation?; (iii) what is energy-saving and COasticity . Finally2es relationship; Mondal et al. [2es relationship; Miah et al. [2es; Shahbaz et al. [2es; Habib and Chungpaibulpatana [2es from various fuels. Moreover, economic growth speed up the process of industrialization, such as agriculture, transport, manufacturing and mining [A large number of research studies have been carried out in Bangladesh with various econometric techniques in analyzing the energy and economic relationship. For example, Bala  employedl et al.  used theh et al.  employedh et al.  applied z et al.  employedulpatana  used sceulpatana  applied d mining ; Usman ed mining  analyzedd mining  estimated mining  investigMeasuring the factor substitutability is necessary for estimating energy and ecological policies. There are numerous measuring techniques for energy substitution elasticity. Thompson  examinedIn general, there exist ‘3’ kinds of relationships between energy and non-energy inputs, i.e., complementarity, substitutability and uncertainty. Precisely, keeping economic production constant, the rise in non-energy inputs will affect energy consumption to perform ‘3’ various roles, i.e., decline, rise and uncertainty. For instance, in the related literature, Adetutu  examinedThe translog production function being the second-order differential equation at a definite point where functional forms charge no boundaries or restriction on the production process has further advantages: (a) avoids utilizing the factor prices' data (b) generally applied to study inter-factor substitutability and (c) have no conditions on first or second differentiation at the point of estimation. For instance, Raza et al.  analyzedFrom Bangladesh’s perspective, very few studies have been found on the subject  based on various models, as discussed above. Moreover, the literature review earlier has given studies of energy substitution based on various types of methods. Though, we did not find the literature on energy and non-energy factor substitution in the transport sector of Bangladesh. The current study assessed the energy substitution, including labor, capital and transport energy consumption using translog production function during 1990–2019. Thus, the study suggests policies for enhancing energy policies, energy conservation and carbon reduction from the transportation sector. Consequently, this study may make up for the gap based on the corrected formula.33.1The employed function (translog production function) is a kind of quadratic response surface model in the context of the structure. This function can be utilized to investigate the interface between input factors in the production process. In addition, this method has both linear and quadratic terms with the capability of employing more than ‘2’ inputs, and it can be estimated to employ the 2nd order Taylor series . In the As per the above expression in Eq. As per Eq. 3.2Multifactor substitutability of various factors using the translog production function is an addition to the CES or Cobb-Douglas function approach. The principal enhancement is that it permits the substitution elasticity to change with the percent of input factors, while the substitution elasticity between various pairs of inputs provides an imperative benefit. As substitution elasticity is a primary indicator to analyze the association between pairs of input factors , which cIt can be noted that “ij” is the pair of factors, i.e., K.L, K.TEC and L.TEC. Given the assumption that firms in the Bangladesh transport industry are cost-minimizing agents, Eq. From Eq. As per Eq. From Eqs. 3.3The model could suffer from multicollinearity issues as a result of the interaction and squared terms of the input variables in Eq. d et al. , the OLSThis condition of multicollinearity can grow, for instance, when statistics are composed without an experimental pattern. To answer this issue, the ridge regression method was adopted, which was proposed by Hoerl and Kennard  and Hoer4t is capital stock, Kt−1 is the previous year’s capital stock, It is the current capital investment, and δ is the capital depreciation rate. K0 and I0 are the initial capital stock and capital investments. ‘g’ is the average growth rate of capital investment from 1990 to 2019. As per Bangladesh’s investment policies, a 5% depreciation rate is taken [In respect of the employed model, four major variables have been used in this study, including the output variable (Y) and inputs capital, labor, and energy consumption in Bangladesh’s transport sector. We analyzed these variables using the aggregate production function output with energy use, labor and capital variables that affect production throughout 1990–2019. In addition, Bangladesh is hugely dependent on fossil fuels, with little renewable energy for production, which could be a significant limitation. The physical capital, labor and energy consumption, we follow the standard growth model and expect that these factors positively impact economic development. For instance, Solow  in the nis taken , which his taken  for Chinis taken  for Pakiis taken  for SoutActually, this method (PIM) was first suggested by Goldsmith  and was 55.1Specified the number of measured parameters in the current translog production model, we started our analysis to estimate the multicollinearity issue in the data using the Kmenta  method. Thus, the multicollinearity problem can be verified through the Variance Inflation Factor (VIF). As per the general principle, if the VIF is larger than 10, the multicollinearity will be severe. If the VIF is higher, then the ridge regression technique could be employed to reduce it; thus, to confirm whether there is a multicollinearity issue in the data, we need to see the VIF of the individual independent variables in the model. As shown in Generally, optimal statistics of ridge parameter (k) exist for the ridge regression model. The assumptions show: (1) if the k-value is very lower; the bias is relatively lower, and (2) if the k-value is higher, the bias is higher. Presently, our objective is to make the bias and VIF both as lower as possible; therefore, this is the dilemma. As per related econometric literature, a few scholars , capital-transport energy consumption (K-TEC) and labor-transport energy consumption (L-TEC) are provided in 5.42es reduction of substitutability between energy and capital investment in Bangladesh’s transport sector. Following Lin and Raza [2es reduction potential are estimated under various scenarios, as demonstrated in 2es reduction would reduce by 3653, 3650 and 3541 MtCO2. On the other hand, a 10% rise in capital stock investment in energy-saving would lessen energy usage by 4.2104, 4.5887 and 4.4520 Mtoe. As a consequence of energy-savings, the CO2es would decline by 0.3827, 0.3823 and 0.3710 MtCO2 during 2017–2019. This emphasizes the efficiency of Bangladesh’s transport sector to obtain energy-saving and carbon reduction. Because of little variation within energy-savings and CO2es reduction  are raising the return to scale. Although, being an under-developing nation, the output of each factor is slightly moderate, which presents a potential for Bangladesh’s transport sector, particularly in investment and energy-conservation.2.2es and reducing fossil fuels.The study analyzes the elasticity of substitution between a pair of factors’, i.e., capital-labor, capital-energy and labor-energy of the transport sector. This shows that all the pairs provide significantly increasing outcomes, with averagely of 1.78, 0.84 and 1.06 indicating that each pair in the study are a substitute. As the output grows in which energy presents a higher degree of responsiveness, flowed by labor and capital. The maximum proportion of labor-capital and labor and energy would be more appropriate for the country’s development. To see the average tests between these factors, all tests rejected the null hypothesis and the average energy is about one at the level. This proposes comparatively higher substitution potential between the pairs of factors. These results are also consistent with Bangladesh Economic Review [3.2es reduction, including the higher investment in energy-related technologies. This will advantage energy-saving, living standards, lessen costs, and increase employment. This suggests that there is a growth in technology and energy, which will reduce subsidies for growth capital.For the conservation of energy and carbon emissions reduction in the transport sector, the current scenarios show that the substitution elasticity between capital investment and energy presents positive efficiency of energy-savings and CO4.Finally, the relative difference in technological progress is majorly input-driven and seems quite gradual changing between 1% and 14%. Overall, the progression between factors is mixed, in which labor-energy is faster than the other pairs of factors. This endorses that energy investment speed is faster than labor and capital. Moreover, a strong convergence between factors is shown, which may enhance and control each factor in the future.The present study analyzes the inter-factor and inter-fuel substitution between labor, capital and energy consumption in the transport sector of Bangladesh. This research applied time-series data from 1990 to 2019 using the trans-log production function method. Due to the multicollinearity issue in the data, we employed ridge regression to control the phenomenon. The results show that:6.22e reduction and enhancing energy security are provided.(a)2es after the industrial and power sector can play an important role. In respect of the highest substitution elasticity between Bangladesh finds itself in a state of plight, and it has to govern its future energy policy rightly. Organizing Bangladesh’s transport sector, the maximum oil consuming sector and the third CO(b)2es [The elasticity of substitution between te CO2es ,52. Usinte CO2es . In addite CO2es  for the te CO2es  for ChinThe significant policies, particularly in the framework of global protest for COFinally, the study is not without limitations. (i) The online availability of statistics should be made sure in the future. (ii) One of the limitations of this is that this model only concentrates on the overall transport, energy, capital, and labor for Bangladesh as a whole. However, the proposed analysis is generic and can be used for any other transport, which is creating more pollution, for example, road transport or air transport and transport link with the public. (iii) Moreover, the causal relationship and co-existence between the variables can be explored in the future. Finally, further study can be made on the accessibility of transportation’s labor, capital, trade transport and non-registered transport companies statistics is also our limitations for future study.Muhammad Yousaf Raza: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.National Natural Science Fund of China (Grant No. 21BJY113).This paper is supported by Data will be made available on request.The authors declare no conflict of interest.


N = 92 subjects with overweight and obesity  of this randomized controlled trial, which were assigned to an interactive (ONLINE: intervention group) or non-interactive (CON: control group) web-based weight loss program, were included in the data analysis. COVIDAge and cardiometabolic risk factors, including anthropometric outcomes, blood pressure, flow-mediated dilatation, and blood parameters, were assessed before and after the 12-week intervention phase. There was a significant group difference in the change of COVIDAge . The ONLINE group also showed significantly greater reductions in anthropometric outcomes and systolic blood pressure than the CON group (p < 0.05). To the authors' knowledge, this was the first study investigating the effects of regular attendance in a web-based health program on lifestyle-related risk factors for COVID-19. The results demonstrated that adults with overweight and obesity can improve their COVIDAge and specific cardiometabolic risk factors by using this interactive web-based weight loss program regularly. However, this needs to be confirmed by future studies. This study is registered at the German Clinical Trials Register .The coronavirus disease 2019 (COVID-19) pandemic has induced unhealthy lifestyles, particularly an increase in overweight and obesity, which have been shown to be associated with an increased risk of unfavorable COVID-19 outcomes. Web-based health programs could be a helpful measure, especially in times of severe restrictions. Therefore, the present study aimed to investigate the effects of regular attendance in a 12-week web-based weight loss program on COVIDAge, a new construct for risk assessment of COVID-19, and lifestyle-related cardiometabolic risk factors.  In late 2019, the first coronavirus disease 2019 (COVID-19) cases caused by severe acute respiratory syndrome coronavirus type 2 were discovered in China , 4.Consequently, dietary and physical activity behavior could change in health-compromising ways during phases of quarantine, isolation, or lockdown . Recent To counteract weight gain and increased cardiometabolic risk, besides the well-known advice to maintain a healthy lifestyle, people should consider participating in web-based weight loss programs . EspeciaTo investigate the influence of lifestyle-related risk factors for COVID-19, a construct accounting for the heterogeneity of risk factors is needed. The COVIDAge Risk Calculator™  represenhttps://www.drks.de). Detailed study information can be found in the published study protocol   ranging from 27.5 to 34.9 kg/ml media) .All recruitment efforts focused on directing interested subjects to a landing page to inform and register for the study, including a written informed consent form. Subsequently, participants were screened by telephone regarding the inclusion and exclusion criteria. After successful screening, an appointment was fixed for the first medical examination. Seven days after this examination, participants were given access to a 12-week web-based weight loss program. The second medical examination was realized after program completion .The program delivered to the intervention group (ONLINE) was one of the coaching modules (“TK-WeightLossCoaching”) of a multimodal health program  offered by a national statutory health insurance fund (Techniker Krankenkasse). With an interactive, self-directed, and flexible usability, this program enables personalized health coaching according to the users' health profiles . The priFor program setup, users first completed a multi-step anamnesis and set their personal weight loss goal (3 or 5 kg). They were then taken to an online platform made up of three areas. The first area  displayed a personal dashboard as a weekly and an overall 12-week coaching plan  that users compiled and modified according to their individual needs. Thereby they could choose from a wide range of mainly 12 weight loss activities, such as “I achieve a green energy density” or “I eat fruit two times and vegetables three times a day,” to be supported in implementing the energy density concept and the principles of a balanced, healthy diet. One preset daily activity was the nutritional protocol, as it was the main activity of the weight loss program. It provided a helpful management tool on energy density, calorie balance, and fluid intake and included an analysis of macronutrients and lots of healthy recipes. Another preset weekly activity was to report body weight and waist circumference. All completed activities had to be logged daily or weekly. Moreover, the dashboard featured current health goal achievements (weight and waist circumference loss), daily tips, notifications, and support opportunities. The second area (“Knowledge”) supplied scientific background information on different health topics  through interactive knowledge courses with texts, videos, tools, and tests. One course (“Weight loss with energy density concept”) was an integral part of the coaching plan to teach users the energy density concept. Finally, in the third area (“My data”), users could view an analysis profile of logged activity data as well as their personal and health profile data, study information including written informed consent, and the option to withdraw study participation. To monitor physical activity behavior, users received an activity tracker (Fitbit Charge 3™) and could synchronize it with the program. At the end of the program, users obtained a coaching summary of their achieved successes .The program was provided as a web-based version that could be used on various electronic devices, such as computers, laptops, tablets, or smartphones. This made the program easily accessible to users anywhere and at any time. Furthermore, the users could adapt the program flexibly to their individual needs, which kept the program interesting and varied. In addition, the program tried to accompany the users in everyday life by providing daily activities, tips, and notifications. All these factors together should increase the acceptance and success of the program. On the other hand, there were some potential barriers to program acceptance and success. Because the program was designed on a scientific, evidence-based foundation, the program usability could be perceived as quite complex. Consequently, program use could be considered time-consuming. This could be very challenging, especially in times of the COVID-19 pandemic in a stressful private and professional situation.The control group (CON) program was similarly designed as an online platform to assist users in losing and maintaining weight over a 12-week intervention phase. However, this program merely offered a health-related knowledge transfer. Therefore, the first area  presented only evidence-based information on various health topics, particularly on the energy density concept and a healthy diet. These contents were taught in small lessons and without any interactive components. In the second area (“My data”), users got personal data, study information, including written informed consent, and the option of withdrawing study participation. For monitoring physical activity behavior, participants of the control group also received an activity tracker (Fitbit Charge 3™) but could not link it to the program. After study completion, access to the interactive web-based weight loss program was provided .https://calculator.covid-age.com) (The primary outcome (COVIDAge) comprised a construct newly developed during the COVID-19 pandemic by Everist Health to estimate an individual's risk for complications of COVID-19 infection . It coveage.com) , conside1c) and blood lipid  levels were taken from blood samples. Furthermore, diseases, medication, and daily cigarette consumption were asked via anamnesis. In order to perform these examinations in a standardized manner, participants appeared fastened , and all examinations were preferably performed at the same time of the day , bioelectrical impedance analysis scale (seca mBCA 515), and measuring tape (seca 201) . Flow-me4, bioele the day .*Power software (Version 3.1) (RRID: SCR_013726)  using the G_013726) . Assumin_013726) , 30 as wol group , 21.With successful online registration, participants were immediately assigned to the intervention and control group by permuted block randomization with variable block sizes of 4, 6, and 8 and an allocation ratio of 1:1. The random allocation sequence was generated by the Section of Health Care Research and Rehabilitation Research of the Medical Center of the University of Freiburg using the RITA software (Version 1.50) . The seqThe study participants could not be blinded due to study information, i.e., the allocation to an interactive and non-interactive web-based weight loss program. In contrast, the clinical trial's healthcare providers and outcomes assessors could be blinded as they would know about group allocation only after data collection was completed. Nevertheless, it could not be ruled out that study participants might report allocation at the medical examinations. The data analysts also could not be blinded because group allocation might have been suspected on the data , 21.t-tests were calculated to compare both groups. For secondary outcomes analyses, repeated measures analyses of variance were computed.For all statistical analyses, the IBM SPSS Statistics software (Version 27.0.0.0) (RRID: SCR_019096)  was usedThe level of significance was set at 0.05 for all comparisons. Participants of the intervention group with a program adherence of ≤ 50%  were excluded from the analysis. This was done to examine program effectiveness based on regular attendance in the weight loss program. Thus, our aim was not to investigate the dose-response relationship within the weight loss program but to examine the effects of a regularly used weight loss program compared to a control intervention. The following data are presented as mean ± SD if not indicated otherwise.N = 53 of the intervention and control group, respectively, had already completed the second medical examination at the time of data analysis. In total, n = 7 dropouts were reported in each study group. None of the dropouts was associated with any side effects of the study. There were also no adverse events reported in either study group. For the following analyses, participants of the intervention group with an adherence rate of > 50% were included (n = 39). Details of the study participant flow are illustrated in p > 0.05).Study participants were recruited from January to July 2020. After randomization and successful screening, they attended the first medical examination and the second after completing the 12-week weight loss program. p = 0.037, d = 0.446; From pre to post intervention, the ONLINE group decreased COVIDAge by −4.2% from 23,152 ± 6,073 days (~ 63.4 years) to 22,178 ± 5,761 days (~ 60.7 years). In contrast, a decline of −1.3% in COVIDage was observed in the CON group . There was a significant group difference  were observed in any other lifestyle-related cardiometabolic risk factor  in adults with overweight and obesity.The construct of COVIDAge has been designed to indicate COVID-19 severity and risk of associated complications. The scale incorporates all major determinants and relies on recent scientific data, including the 10 year Framingham study . This siDuring the COVID-19 pandemic, the importance of home-based health programs significantly increased. Implementing non-pharmacological countermeasures, such as lockdowns or orders to stay and work at home, has essentially contributed to reducing the spreading and thus mortality of COVID-19 , 36. Fron = 57 people participated in a 12-week weight loss program. The modules included individualized sessions addressing dietary and exercise modifications. Additionally, two groups received a web-based program to monitor eating habits and a wearable device monitoring energy expenditure. For both online groups, these features were provided either continuously or intermittently  during the intervention . The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication The article processing charge was funded by the Baden-Wrttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding program Open Access Publishing.JB and DK report funding from Techniker Krankenkasse for the study design, implementation, and evaluation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The high value area for CS was concentrated mainly in forest land, water body and grassland, whereas the low value area was concentrated mainly in construction land. During 2000–2015, CS decreased by 0.23 Tg, and during 2015–2050, CS was predicted to decrease by 0.16, 1.69, 0.02, and 0.10 Tg under the baseline, fast, slow and harmonious development scenarios. The conversion of a large amount of cropland to construction land was the main cause of CS loss. In all scenarios, the carbon loss was the largest in southern Jiangsu and lowest in central Jiangsu. It is necessary to balance the conflict between economic development and ecological protection during the process of urbanization. This study can provide an important reference for decision makers during the formulation of regional development models and ecological management strategies.Carbon storage (CS) is closely linked to the global challenge of climate change. Land use/cover (LULC) change is the main factor driving changes in CS, and evaluating the impact of LULC changes on CS is important for carbon balance. Taking Jiangsu Province as an example, we used the Integrated Valuation of Ecosystem Services and Trade-offs model to analyze the spatiotemporal changes in CS during 2000–2015. Then we coupled it with the patch-generating land use simulation model to simulate and predict LULC and CS in 2050 under four different development plans. The results showed that LULC change in Jiangsu Province was manifested mainly as transformation of cropland to construction land (3,485 km Terrestrial carbon is an important element of global carbon storage (CS) and plays a critical role in carbon dioxide-driven climate change . ChangesEcosystem services are an important guarantee of human well-being and sustainable economic and societal development . RecentlChina is going through a phase of rapid urbanization, and balancing the speed of urbanization with CS is an important issue for high-quality regional development . UnderstIn this study, we selected Jiangsu Province as a typical region for quantitatively assessing CS in response to different needs during city development. We designed four urbanization scenarios with local city planning and land policies to explore the drivers of spatiotemporal LULC changes. The study aimed to (1) analyze changes in LULC and CS from 2000–2015; (2) predict future changes in CS under different development scenarios; and (3) propose an appropriate LULC layout that can produce win-win results, balancing urban development and CS enhancement. This study can provide suggestions to policy-makers and stakeholders for improving sustainable urbanization in their area.4 km2 in area, with 13 cities and 63 counties. The topography is mainly plains, which account for 68.8% of Jiangsu Province. The region has a subtropical monsoon climate with a mean annual temperature of approximately 15.1 °C and an average annual precipitation of 1,002 mm (Jiangsu Province (30°45′N–35°20′N and 116°18′E–121°57′E) is located in eastern China in the lower reaches of the Yangtze River, with Shandong Province to the north, Zhejiang Province and Shanghai City to the southeast, and Anhui Province to the west . This pr1,002 mm . Jiangsu Province has faced considerable pressure to balance ecosystem services with rapid urbanization. In 2020, the total population of Jiangsu was 84.75 million, and its gross domestic product (GDP) was 10.27 trillion yuan. Based on the economic development status of the cities in Jiangsu, we divided the study area into three subregions: southern Jiangsu (SJ), central Jiangsu (CJ), and northern Jiangsu (NJ). Rapid population growth and gradually increasing regional inequality have made Jiangsu a more typical case study than other Chinese provinces for the assessment of changes in CS under urbanization and for the simulation of future CS changes. It provides a research test case for developing countries that face rapid urbanization.http://www.resdc.cn/). Data producers evaluated the accuracy of LULC based on field surveys, visual interpretations and obfuscation matrix judgments, and the results showed that the overall interpretation accuracy of LULC was over 90% (http://data.tpdc.ac.cn). Slope was calculated from the DEM in ArcGIS 10.3 software. Road, river, railway, and highway data were acquired from the National Earth System Science Data Center (http://www.geodata.cn/). The data used in the study are also shown in LULC, precipitation, temperature, GDP, population (POP), and normalized difference vegetation index (NDVI) data with a spatial resolution of 1 km were obtained from the Data Center for Resources and Environmental Sciences of the Chinese Academy of Sciences  model estimates the CS based on the aboveground biomass, underground belowground biomass, soil organic matter, and dead organic matter carbon pools. The InVEST model evaluates the CS of each pixel based on the LULC type and the corresponding carbon density. The calculation formula is as follows: Ctotal, Cabove, Cbelow, Cdead, and Csoil are the total CS, aboveground carbon storage (AGC), belowground carbon storage (BGC), soil carbon storage (SOC), and dead carbon storage (DOC), respectively. In this study, the carbon density data for the different LULC types were obtained from the field and from some previous studies in Jiangsu Province , the quantity of LULC types in each scenario was determined  and cropland to water body (470 km2).The composition of LULC types in Jiangsu Province from 2000 to 2015 showed that cropland was the most abundant LULC type, accounting for more than 65%, followed by construction land and water body . Bare laCS changed significantly between 2000 and 2015, especially in SJ . The hig2 in 2000 to 944.84 Mg/km2 in 2015. The CS in SJ accounted for approximately 28% of the Jiangsu Province; it also decreased the most, from 27.10 Tg in 2000 to 26.97 Tg in 2015. Because CJ had the smallest area in Jiangsu Province, it also had the lowest CS, accounting for only 20% of the total CS and declining by 0.03 Tg from 2000 to 2015. NJ accounted for 51% of the CS in Jiangsu, and this only decreased from 48.62 Tg to 48.56 Tg between 2000 and 2015. The reduction in CS was greatest in SJ (0.13 Tg) and lowest in CJ (0.03 Tg). Regions with significant reductions in CS were located mainly in Suzhou City, the middle of Nanjing City, and Changzhou City. However, CS increased significantly in the south of Nanjing City, the south of Wuxi City, the north of Yangzhou City, the south of Suqian City, and the middle and north of Huai’an City. The reduction rate of CS in Jiangsu decreased from south to north: SJ had the highest rate, and NJ had the lowest.The total CS in 2000 was 95.58 Tg, and it decreased by 0.23 Tg from 2000 to 2015 . The aveLULC change is the main driving factor affecting CS. The loss of CS from 2000 to 2015 was mainly caused by a loss of SOC, which decreased by 0.22 Tg; in contrast, AGC only decreased by 0.01 Tg . CroplanChanges in CS from 2000 to 2015 in Jiangsu were caused primarily by the following LULC conversions: cropland to forest land, water body, and construction land; forest land to construction land; and water body to construction land, cropland, and bare land. The conversion of cropland to construction land led to great losses in CS, and the total CS decreased by 0.22 Tg. The conversions of forest land to construction land and water body to construction land, cropland, and bare land caused CS losses of 0.04 Tg, 0.03 Tg, 0.02 Tg, and 0.01 Tg, respectively. Therefore, the loss of CS was caused mainly by urbanization. The conversion of cropland to forest land and water body was associated with CS increases of 0.01 Tg and 0.07 Tg during 2000–2015. In other words, ecological restoration projects such as returning farmland to forests and lakes increased some CS, but they did little to reverse the overall carbon loss caused by urbanization.Under the FD scenario, reductions in cropland, forest land and grass land resulted in carbon losses of 5.92, 3.14, and 0.50 Tg, respectively. CS declined in all counties, among which Jiangning District, Jurong City, Yixing City, and Tongshan County had significant carbon losses. The same pattern of development occurred under the BD scenario, albeit at a slower urbanization rate than under the FD scenario. Because of the huge population pressure and rapid economic growth, the increased demand for urban infrastructure construction and urban area led to carbon loss under the FD and BD scenarios. In the BD scenario, carbon loss was still greatest from cropland (0.84 Tg), but the carbon loss from grassland (0.26 Tg) exceeded that from forest land (0.17 Tg) and became the second largest carbon loss. In both scenarios, more than half of the carbon loss came from the loss of cropland.The distribution of CS under the SD scenario was similar to that under the BD scenario, but the carbon loss under the SD scenario was lowest. Because of slow economic and population growth in this scenario, the urbanization process was slower than that under the BD scenario. Under SD, the expansion of cropland consumed the least amount of forest land and grassland. Thus, the impact of grassland and forest land loss on CS reduction was minimal under SD relative to other scenarios. Although the reduction in grassland under SD was smaller than that under the other scenarios, the carbon loss from grassland (0.06 Tg) exceeded that from cropland (0.05 Tg) as the main source of carbon loss. Social and economic development had different influences on these scenarios: the HD scenario still maintained a pattern of forest land and grassland similar to that of SD, and reasonable plans for urban land expansion reduced the environmental pressures caused by increasing demands of social and economic development. Forest carbon loss under the HD scenario was similar to that under the BD scenario, but grassland carbon loss was lower than that under the SD scenario. In the HD scenario, although the city continued expanding, the loss of ecological land was reduced, and economic development was to some extent balanced with ecological protection.Rapid urbanization and population concentration have inevitably encroached on other ecosystem types, including woodland, cropland, and grassland . TherefoSome studies have shown that combining CS simulation model with land use prediction model can effectively simulate potential changes in CS caused by future urban expansion . Here, wBecause of the different developmental stages of urbanization in SJ, CJ, and NJ, it is important to propose economic development and ecological protection policies based on their individual characteristics. In SJ, with a growing population and increasing urbanization, a large amount of cropland and water body have been converted to impervious surfaces that cause significant degradation of ecosystem services. Hence, the protection of other types of ecological land, including wetlands and water body, should be enhanced by appropriate policies. In CJ, it is essential to strengthen the control of urban expansion and mitigate the enormous pressures on ecosystem services caused by population growth. At the same time, we should pay attention to the proportion of ecological land converted to impervious surfaces. In NJ, we need to raise the level of economic and social development, but at the same time, strict policies and measures should be taken to protect cultivated land and water body. Most importantly, enhancing regional ecosystem services requires comprehensive initiatives for the rational use of land resources and socioeconomic development.e.g., biodiversity, flood regulation, and soil retention. Hence, we should simulate multiple ESs under different scenarios and assess the temporal and spatial variations in these ESs in addition to CS. Since the latest LULC data have not been obtained, this study only analyzed the changes of CS from 2000 to 2015. In the future, yearly LULC data from 2000 to 2020 can be used to better reveal the dynamic changes in CS in the past. Additionally, the spatial resolution of the remote sensing images used in this study was 1 km, which may have impacted the simulation accuracy. We could use high-accuracy remote sensing imagery  to classify land-use type changes and obtain more accurate simulation results. Moreover, some important factors that may impact CS were not considered in this study; these include human cultivation habits, management methods, seasonal changes, and vegetation growth. These factors may introduce some uncertainties into the simulation results.Combining the PLUS and InVEST models is useful for simulating CS change under different scenarios. However, some limitations of the present study may benefit from further improvements. First, as urban development expands, many ecosystem services are compromised, We chose Jiangsu Province—one of China’s most urbanized provinces—as a case study to analyze changes in CS during 2000-2015 and to explore the impact of socioeconomic and policy interventions on CS under four development plans. Combining the PLUS and InVEST models is an effective means of predicting future changes in CS under different scenarios. Jiangsu Province experienced CS losses of 0.23 Tg from 2000 to 2015 and is predicted to experience further CS losses of 0.16, 1.69, 0.02, and 0.10 Tg from 2015 to 2050 under the BD, FD, SD, and HD scenarios. The CS in construction land increased, whereas that in cropland, forest land, and grassland decreased. The predicted CS losses from 2015 to 2050 were greater in SJ than in CJ and NJ; SJ had the greatest carbon loss rate and NJ had the smallest under all scenarios except for FD. Although land use conversion patterns differed among SJ, CJ, and NJ, the main driving factor causing CS losses was the transformation of cropland and ecological land into impervious surfaces. Ecological restoration projects can offset some of the CS loss caused by urbanization. Future land use strategies must balance the conflict between economic development and ecological protection. Therefore, it is necessary to optimize urban planning in different areas by considering land use patterns holistically to achieve sustainable development. The protection of ecological land should be strengthened in SJ, the control of the urban expansion rate should be strengthened in CJ, and the social and economic development should be improved in NJ. This study can help local governments contribute to green urban development and carbon emission reduction.10.7717/peerj.13411/supp-1Table S1Click here for additional data file.10.7717/peerj.13411/supp-2Table S2Click here for additional data file.10.7717/peerj.13411/supp-3Table S3Click here for additional data file.10.7717/peerj.13411/supp-4Supplemental Information 1Open using ArcGIS.Click here for additional data file.


Although primary care (PC) is an indispensable part of the health system, measuring its quality is challenging. A recent measure of PC, Person-Centered Primary Care Measure (PCPCM), covers 11 important domains of PC and has been translated into 28 languages. This study aimed to develop a Japanese version of the PCPCM and assess its reliability and validity.We employed a cross-sectional mail survey to examine the reliability and content, structure, criterion-related, and convergent validity of the Japanese version of the PCPCM. This study targeted 1000 potential participants aged 20–74 years, selected by simple random sampling in an urban area in Japan. We examined internal consistency, confirmatory factor analysis, correlation between the Japanese version of the Primary Care Assessment Tool-Short Form (JPCAT-SF), and the association between the PCPCM score and influenza vaccine uptake.A total of 417 individuals responded to the survey (response rate = 41.7%), and we used the data of 244 participants who had the usual source of care to assess the reliability and validity of the PCPCM. Confirmatory factor analysis demonstrated sufficient structural validity of the original one-factor structure. The overall Cronbach’s alpha was 0.94. The Spearman correlation coefficient between PCPCM and JPCAT-SF was 0.60. Influenza vaccine uptake was not significantly associated with total PCPCM score.The study showed that the Japanese version of the PCPCM has sufficient internal consistency reliability and structural- and criterion-related validity. The measure can be used to compare the quality of primary care in Japan and other countries. Primary care (PC) is an important part of the healthcare system because it is associated with the effective use of healthcare resources and health equity –4. PC coTo overcome these problems, Etz et al. developed in the United States the Person-Centered Primary Care Measure (PCPCM) in 2019 . In partIn Japan, the Japanese version of the Primary Care Assessment Tool (JPCAT) has been widely used to assess the quality of PC –16. JPCATherefore, this study aimed to develop a Japanese version of the PCPCM and assess its reliability, content, structural, criterion-related, and convergent validity.We conducted a cross-sectional study using a mail survey to assess the reliability and validity of the Japanese version of the PCPCM. Reliability was evaluated by internal consistency, and the validity assessment included content, structural, criterion-related, and convergent validity.Using simple random sampling, we selected 1000 potential participants aged 20–74 years using a basic resident register. The sampling site was Konan-ku, located in the city of Yokohama, Japan, because this area has a similar proportion of people aged 65 years and older (28.6%), and people who receive government safety net programs for livelihood, housing, and healthcare services (1.5%) compared to overall Japan . YokohamThe participants answered questions about the Japanese version of the PCPCM, JPCAT-SF, age, sex, years of education, household income, self-rated health, number of years the patient had been with the physician, number of years the patient had been with the practice, and influenza vaccination status. Data were collected between August and September of 2021. Regardless of whether the recipients of the survey responded, the participants also received small gifts worth 500 JPY (approximately 5 US dollars).https://www.green-center.org/pcpcm.In accordance with the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures , we deveAs with the original PCPCM, the Japanese version consists of 11 questions: accessibility, comprehensiveness, integration, coordination, relationship, continuity, advocacy, family context, community context, goal-oriented care, and health promotion . Each itBecause the role of general practitioner/family physicians is ambiguous in Japan , patienthttps://www.r-project.org).We examined the psychometric properties of the Japanese version of the PCPCM using the following steps based on the COSMIN Study Design checklist for patient-reported outcome measurement instruments . First, To examine the properties of the PCPCM and perform a satisfactory factor analysis, we estimated a minimal sample size of 200 residents who have USC , 33. BasA total of 417 individuals responded to the survey (response rate = 41.7%). However, 14 were excluded by a blank ballot; thus, the study was conducted on the remaining 403 respondents. The respondents were older than the non-respondents , and men were less likely to participate in the survey than women . Of the 403 individuals, 244 (60.5%) had USC. Table p = 0.8626). Moreover, in the logistic regression analysis, the PCPCM total score was not statistically significantly associated with influenza vaccine uptake: OR per 1SD was 1.19 . However, coordination and advocacy were positively associated with vaccine uptake: OR per 1SD 1.37 , OR 1.40 , respectively. In the same dataset, the JPCAT-SF total score was also not associated with vaccine uptake: OR 1.02 . Table Figure The overall Cronbach’s alpha coefficient of the PCPCM was 0.94, and the Cronbach’s alpha coefficient for all items was > 0.90. The item-total correlation ranged from 0.66 –0.80.In the present study, we developed a Japanese version of PCPCPM that showed sufficient internal consistency, reliability, and structural and criterion-related validity. In terms of convergent validity, vaccine uptake was not significantly associated with the total PCPCM score. However, the PCPCM had sufficient reliability and validity for assessing patient experience in PC in the Japanese setting.Zyzanski et al. Examined the psychometric properties of the Japanese version of the PCPCM in 35 The Organisation for Economic Co-operation and Development (OECD) countries, including Japan . HoweverRegarding the results of confirmatory factor analysis, RMSEA did not meet the criteria set a priori. However, other evaluation standards fulfilled the criteria. Therefore, we regarded the structural validity as sufficient. In criterion-related validity, the correlation coefficient between the score of the PCPCM and the JPCAT was the border between moderate and strong . This miIn terms of the PCPCM score, the mean total score in our study was 2.59. This was slightly higher than Zyzanski et al.’s reported score of 2.46 . A possiAlthough our version of the Japanese PCPCM showed sufficient internal consistency reliability, criterion-related validity, and construct validity, convergent validity demonstrated inconsistent results when compared to previous studies that used other patient experience measures , 28. EveThe PCPCM can assess various aspects of PC and compare the results with those of other countries. The PCPCM has been translated into 28 languages and has assessed reliability and validity in 35 OECD countries . TherefoOur version of the Japanese PCPCM was developed by a research team that included native Japanese PC physicians, PC researchers, and a bilingual physician who practiced medicine in Japan, the United Kingdom, and the United States, which This is useful for creating an understandable measure for the Japanese native population. Moreover, because this study employed a mail survey and recruited randomly selected adults from the general population, compared to the previous Japanese version, the results of our study could be generalised to people in other areas of Japan. In addition to the previous Japanese version by Etz et al. , this stOur study has several potential limitations. First, measurement errors such as test-retest reliability and responsiveness were not assessed because of difficultiy of conducting follow-up survey, and convergent validity and discriminant validity were not confirmed by hypothesis testing. Second, non-response bias may have affected the results. Individuals with negative past PC experiences might not have responded to the survey. Therefore, respondents might have given a higher score than non-respondents, and patient experience in Japan may have been overestimated. Third, our study was conducted in an urban area. Although we selected the study area based on the proportion of the older population and people who received public assistance, other factors were not considered. Thus, the results need to be interpreted carefully. A survey on the PCPCM in other settings such as a rural area should, therefore, be conducted in the future.The alternative version of the Japanese PCPCM showed sufficient reliability and validity. Our version was created specifically for Japanese patients by Japanese physicians/researchers and can be used to compare the quality of PC in Japan and in other countries. Understanding the strengths and weaknesses of PC in Japan is important for effective PC development.


To compare the clinical efficacy of robot of stereotactic assistant (ROSA) and frame-assisted stereotactic drilling and drainage for intracerebral hematoma in hypertensive intracerebral hemorrhage (HICH).A total of 142 patients with HICH treated in Baoding First Central Hospital from January 2018 to January 2020 were selected and divided into two groups using a random number table. The ROSA group was treated with a robot of stereotactic assistant, while the frame group underwent frame-assisted stereotactic drilling and drainage for intracerebral hematoma. Surgical duration, postoperative extubation time and complications were compared between the two groups. Venous blood (5 mL) was collected before and three days after surgery. The levels of inflammatory factors , as well as neurological function indexes  were detected by enzyme-linked immunosorbent assay.P < 0.05). In the ROSA group, postoperative TNF-α, hs-CRP, IL-6 and NSE levels were significantly lower while NGF and BDNF levels were higher than those in the frame group .The surgical duration, postoperative extubation time, and incidences of infection and postoperative rehemorrhage in the ROSA group were lower than those in the frame group (Compared with frame-assisted stereotactic drilling and drainage for intracerebral hematoma, ROSA in HICH treatment shortens the surgical duration and postoperative extubation time, reduces the risks of infection and rehemorrhage and decreases inflammatory level, which is helpful for the recovery of neurological function. Hypertensive intracerebral hemorrhage (HICH) is a brain disease caused by the rupture of intracranial arteries induced by a sharp increase in blood pressure.A randomized controlled trial was used in this study. A total of 142 patients with HICH treated in Baoding First Central Hospital from January 2018 to January 2020 were selected, aged 21~79 years, average age of (56.51 ± 8.23) years.The study was approved by the Institutional Ethics Committee of Baoding No.1 Central Hospital on May 27, 2021 (No. [2021]068), and written informed consent was obtained from all participants.Patients with the volume of supratentorial hematoma was ≥ 20 mL, or the volume of infratentorial hematoma was ≥ 10 mL in imaging examination;Patients with a history of hypertension and meeting the surgical indications;Patients with Glasgow Coma Scale (GCS) score ≥ 5;Patients or family members signing the informed consent and voluntarily participating in the study.Cerebral hemorrhage caused by rupture of intracranial aneurysm or craniocerebral trauma;Brainstem hemorrhage;Dysfunction of the liver, kidney or other important organs.The 142 patients with HICH were divided into two groups using a random number table, with 71 patients in each group.ROSA group: The surgery was performed using the equipment produced by MedTech, France. The scalp was marked before surgery, and the scalp markers were registered successively after angiography. The surgical entrance was selected under laser guidance. After cutting open the soft tissue, a hole with a diameter of one cm was drilled. After the dura mater was cut open, the puncture needle was introduced with the aid of the mechanical arm, the hematoma was pumped, the drainage tube was placed and then the surgical channel was closed. After surgery, urokinase was injected according to the volume of residual blood. When the volume of hematoma < 5 mL, the drainage tube was removed.The surgery was carried out using the stereotactic frame assistant system produced by Leibinger, Germany. The specific procedure is as follows: Wearing Fisher headframe, the hematoma was located using CT scanning, and the surgical target was determined according to the maximum dimension of hematoma. Based on the established surgical plan, a 4~5 cm longitudinal incision was made at the selected location. After drilling the skull, the dura mater was cross-cut and the puncture needle was inserted with the aid of a navigator. After reaching the target, the hematoma was pumped, the drainage tube was placed and then the surgical channel was closed. Postoperatively, urokinase was injected according to the volume of residual blood. When the volume of hematoma < 5 mL, the drainage tube was removed.The baseline data including gender, age, GCS score at admission, hematoma volume and time from onset to surgery in both groups were counted. Surgical duration, bleeding volume, postoperative extubation time and complications were also recorded. Venous blood (5 mL) was collected before and three days after surgery. The levels of inflammatory factors , as well as neurological function indexes , were detected using enzyme-linked immunosorbent assay.2χ test or Fisher’s exact probability test. The measurement data were expressed as x̅±s, and analyzed by the independent t-test. P < 0.05 was considered statistically significant.The data were analyzed using SPSS23.0. The enumeration data were expressed as rate, and analyzed with the P > 0.05), as shown in P < 0.05). However, no statistically significant difference was found in bleeding volume between the two groups (P > 0.05)  .P < 0.05), as seen in P < 0.05). In the ROSA group, postoperative TNF-α, hs-CRP, IL-6 and NSE levels were significantly lower while NGF and BDNF levels were higher than those in the frame group  (P < 0.05). After treatment, the NSE level was lower while NGF and BDNF levels were higher in the ROSA group compared with the frame group (P < 0.05), as shown in The incidences of infection and postoperative rehemorrhage in the ROSA group were lower than those in the frame group ( < 0.05) . No statHICH is one of the most severe complications of hypertension. Long-term hypertension can cause swelling and lipid precipitation of the vascular intimal matrix, resulting in reduced vascular elasticity, increased brittleness, fibrinoid necrosis and vitreous degeneration of the vascular wall.9Frame-assistant stereotactic drilling and drainage can help HICH patients rapidly remove hematoma and relieve the adverse effects caused by the decomposition products and space-occupying effect of hematoma, thus reducing intracranial pressure and avoiding the progressive development of encephaledema.12In our study, 142 HICH patients were divided into two groups: ROSA group was treated with stereotactic assisted robot, and frame group was treated with stereotactic assisted drilling and drainage of intracranial hematoma. The results of this study found that, compared with the traditional stereotactic frame system, ROSA adjuvant therapy for HICH has the following advantages:The ROSA system is easy to operate, and it operates according to the preset surgical plan without manual calculation, saving the installation time of components. The shortened surgical duration can reduce the exposure time of brain tissue, decrease the risk of infection and improve the long-term efficacy. Which was similar to the research results of Spyrantis A et al.13ROSA system can carry out three-dimensional (3D) reconstruction for the morphology of cerebral hematoma in HICH patients, help surgeons understand the morphological characteristics of hematoma more clearly and intuitively, and facilitate the formulation of personalized surgical plans. The selection of surgical approach is more scientific and reasonable. The inserted drainage tube can coincide with the maximum diameter of hematoma in multiple dimensions. The effect of surgical removal of hematoma is better, and the postoperative extubation time is shorter than that of patients using the stereotactic frame. For surgical approach in HICH patients using stereotactic frame system, because of the unobservable 3D morphology of hematoma, it is impossible to ensure that the drainage tube is inserted completely along the long axis of hematoma, which delays the postoperative extraction time of drainage tube and increases the risk of infection. Which was similar to the results of previous studies.14High safety. ROSA system has larger surgical space and more convenient operation due to no frame interference. With a stereotactic frame system, it needs to wear a headframe before surgery and then conduct CT scanning, which is not conducive to emergency surgery. The dural incision is smaller than that of the stereotactic frame system, which reduces the risk of postoperative pneumocranium, accelerates postoperative recovery and decreases complications. This was similar to the results of Alan N et al.15Previous studies on ROSA mainly focused on its short-term and long-term efficacy, but its impacts on body inflammatory state and neurological function were rarely reported.The number of subjects included in this study was limited, so the conclusions drawn may not be very convincing. In addition, we only analyzed and discussed the cases included in our hospital, which may not be representative enough. We look forward to a multi-center study in the future to reach more comprehensive conclusions.Compared with frame-assisted stereotactic drilling and drainage for intracerebral hematoma, ROSA in HICH treatment shortens the surgical duration and postoperative extubation time, reduces the risks of infection and rehemorrhage, and decreases inflammatory level, which is helpful for the recovery of neurological function.LL & XL: Designed this study , prepared this manuscript, are responsible and accountable for the accuracy, integrity of the work.HD & XG: Collected and analyzed clinical data.GW: Significantly revised this manuscript.