Nevin Manimala

Am J Hum Biol. 2025 Dec;37(12):e70173. doi: 10.1002/ajhb.70173.

ABSTRACT

BACKGROUND: Low birth weight is a critical predictor of child mortality and morbidity, contributing to both immediate health complications after birth and long-term health issues later in life. Globally, it remains a major public health challenge, particularly in low- and middle-income countries, where poor maternal nutrition, limited access to quality healthcare, and poverty exacerbate the risk. Regions such as Sub-Saharan Africa and South Asia carry the highest burden, accounting for the majority of low birth weight cases worldwide. Within this context, Pakistan stands out as one of the countries with the highest rates of child mortality and malnutrition, making the issue of low birth weight especially pressing.

METHODOLOGY: Utilizing the Demographic and Health Survey of 2017-18, multiple analytical techniques were used including logistic regression, standard, Wagestaff, Erreygers concentration index analysis and concentration curves.

RESULTS: The study indicates that low birth weight (LBW) is disproportionately concentrated among socio-economically disadvantaged groups. Negative and significant concentration indices for household wealth, maternal education, and paternal education show that children from poorer and less educated families are at higher risk of LBW. Further analysis reveals that the relationship between household wealth, parental education and LBW is nonlinear in the context of rural-urban division. Rural children from middle and higher-income families show a slightly elevated risk as compared with urban. Similarly, mother’s education seems less effective against LBW. However, father’s education might help as LBW is slightly reduced among higher educated fathers. This counterintuitive pattern may be influenced by factors such as multiple births, cesarean deliveries, antenatal care utilization, or other socio-cultural dynamics. For example rural women might have less decision-making autonomy regarding health and meeting other necessities of life.

CONCLUSION: The study finds that low birth weight (LBW) is disproportionately concentrated among socio-economically disadvantaged groups, with household wealth and parental education serving as strong protective factors. However children from middle and higher-income households, in rural areas, may also experience a slightly elevated risk of LBW as compared to urban populations Father’s education might play a more protective role against low birth weight among rural areas.

PMID:41320666 | DOI:10.1002/ajhb.70173

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4076-4080. doi: 10.3760/cma.j.cn112137-20250621-01515.

ABSTRACT

Objective: To explore the clinical effect of different coronary artery flow isolation methods in off-pump coronary artery bypass grafting (OPCABG). Methods: A total of 60 patients who accepted OPCABG in the Department of Cardiovascular Surgery, the First Affiliated Hospital of Zhengzhou University from June 2021 to June 2024 were randomly divided into three groups by computer. The different coronary flow isolation methods were used in three groups. The coronary artery was occluded with tourniquets in the occlusion group (n=20). The coronary artery was shunted with shunt in the shunt group (n=20). The coronary artery was selectively shunted or occluded according to the different blood flow conditions of each target vessel in the combined group (n=20). The anastomosis time and the amount of bleeding were observed and compared. The serum levels of cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-ProBNP) were detected after eight hours of operation. Results: Among the 60 patients with coronary artery disease, 48 patients were male and 12 patients were female. The anastomotic time of each anastomosis in the shunt group was longer than that in the occlusion group and the combined group [(18.4±2.8) min vs (12.3±2.2) min, (14.3±2.9) min, both P<0.017]. There was no statistically significant difference in anastomotic time between the occlusion group and the combined group (P=0.176). Postoperative serum cTnT in the occlusion group was higher than that in the shunt group and the combined group [(0.28±0.07) μg/L vs (0.16±0.03) μg/L, (0.17±0.04) μg/L, both P<0.017]. There was no statistically significant difference in postoperative serum cTnT between the shunt group and the combined group (P=0.152). Postoperative serum NT-ProBNP in the combined group was lower than that in the occlusion group and the shunt group [(254±27) ng/L vs (481±19) ng/L, (373±42) ng/L, both P<0.017]. Postoperative serum NT-ProBNP in the shunt group was lower than that in the occlusion group [(373±42) ng/L vs (481±19) ng/L, P=0.001]. There were no significantly differences in the amount of bleeding among the three groups (P=0.191). Conclusion: The selected method of occlusion or shunting depending on the flow condition of target coronary artery in OPCABG can decrease anastomosis time and myocardial injury.

PMID:41320662 | DOI:10.3760/cma.j.cn112137-20250621-01515

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4065-4075. doi: 10.3760/cma.j.cn112137-20250901-02267.

ABSTRACT

Objective: This study aimed to comprehensively investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 (SPP1) in the three-stage progression of “smoking-chronic obstructive pulmonary disease (COPD)-carcinogenesis” in lung squamous cell carcinoma (LUSC) through integrated bioinformatics analysis and machine learning. Methods: The datasets for the three stages of LUSC were downloaded from the Gene Expression Omnibus (GEO) database, including GSE18385 (containing lung tissue samples from 31 healthy smokers and 21 healthy non-smokers), GSE38974 (containing lung tissue samples from 23 smoking COPD patients and 9 healthy smokers), and GSE12472 (containing lung tissue samples from 18 LUSC patients with COPD and 17 smoking COPD patients). The Cancer Genome Atlas (TCGA)-LUSC dataset (comprising 504 samples, including lung tissue samples from LUSC patients and their matched normal lung tissue samples) was downloaded from TCGA database for further analysis. Samples and follow-up information from 208 non-small cell lung cancer patients who underwent radical resection and mediastinal lymph node dissection at Zhongshan Hospital, Fudan University in 2005 were selected for prognostic analysis and validation. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to screen stage-specific module genes. Differentially expressed genes (DEGs) were identified through differential expression analysis. The CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were used to characterize the immune microenvironment. Eight machine learning algorithms and protein-protein interaction (PPI) network analysis were combined to screen for core regulatory targets. Results: Results from WGCNA and differential analysis of the GEO datasets indicated that SPP1 is consistently highly expressed across the three stages of LUSC. Analysis of the TCGA-LUSC dataset further verified that the relative expression level of SPP1 in lung tissues of LUSC patients was significantly higher than in normal lung tissues (9.13±2.01 vs 4.68±1.64, P<0.001). Furthermore, SPP1 expression was significantly higher in patients with TNM stage Ⅲ than in those with stage Ⅱ (9.59±2.09 vs 8.80±2.15, P=0.045). Male LUSC patients with high smoking exposure exhibited higher SPP1 expression levels than those with low smoking exposure (9.56±2.23 vs 8.60±2.04, P=0.032). Survival prognosis analysis revealed that among male patients, the difference in median overall survival (OS) between the high SPP1 expression group and the low expression group was statistically significant [2.90 (95%CI: 2.11-4.64) years vs 4.69 (95%CI: 2.95-7.34) years, P=0.032). Data validation from Zhongshan Hospital, Fudan University, also showed that the 5-year survival rate of lung cancer patients with high SPP1 expression was lower than that of patients with low SPP1 expression (49.3% vs 62.6%, P=0.042). Results from the CIBERSORT algorithm indicated that high SPP1 expression drives increased infiltration of M2 macrophages (P<0.001). Machine learning combined with PPI network analysis identified NTN1 and CX3CL1 as key regulatory targets of SPP1, which may be associated with the occurrence and development of lung cancer. Conclusion: SPP1 may promote LUSC progression by mediating M2 macrophage polarization through suppressing NTN1 or activating CX3CL1, suggesting its potential as a prognostic biomarker and therapeutic target for high-risk male smokers.

PMID:41320661 | DOI:10.3760/cma.j.cn112137-20250901-02267

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4056-4064. doi: 10.3760/cma.j.cn112137-20250619-01495.

ABSTRACT

Objective: To construct and validate a prognostic model for patients with advanced lung squamous cell carcinoma (LUSC) receiving chemotherapy combined with immunotherapy based on quantitative CT features. Methods: A total of 96 patients with advanced LUSC who received chemotherapy combined with immunotherapy at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2020 to October 2023 were retrospectively included. They were randomly divided into a training set (n=72) and an internal validation set (n=24) at a ratio of 3∶1 (random sequence was generated by R Studio 4.4.2 software). Additionally, patients with advanced LUSC who visited Yichang Central People’s Hospital from October 2020 to June 2024 were enrolled as the external validation set (n=58) according to the same criteria. Pretreatment chest CT images were obtained from patients, and quantitative CT features were extracted. Based on the training set data, LASSO regression and univariate and multivariate Cox regression models were used to screen the independent variables, and the model was constructed with the progression-free survival (PFS, progress=1, no progression=0) as the dependent variable. Taking the progression at 180 d as the outcome variable and the quantitative CT score as the evaluation index, the receiver operating characteristic (ROC) curve was drawn. The calibration curve and decision curve were used to evaluate the model efficacy. Based on the optimal cut-off value determined by the ROC curve, patients were divided into high-risk and low-risk groups, and the log-rank test was used to compare the survival differences between the two groups. Results: A total of 154 patients with LUSC were included, including 147 males and 7 females, with an age of (64.7±8.1) years; there were no statistically significant differences in demographic characteristics and TNM stage among the training set, internal validation set, and external validation set (all P>0.05). Four quantitative CT features were associated with PFS, including the percentage of low attenuation area with CT value < -910 HU in the whole lung (LAA%-910_lung) (HR=0.013, 95%CI: 0.002-0.313), the area percentage of low attenuation area with CT value < -950 HU in the right lower lung (LAA%-950_right_lower) (HR=0.011, 95%CI: 0.001-0.012), the minimum wall thickness of grade 2 airwall (minThicknessOfAirwall_2) (HR=0.117, 95%CI: 0.029-0.463) and the mean diameter of grade 1 airway (meanDiameterOfAirway_1) (HR=0.767, 95%CI: 0.687-0.857), which were used to construct the quantitative CT (QCT) score: QCTscore=-4.346×(LAA%-910_lung)-4.513×(LAA%-950_right_lower)-2.14×(minThicknessOfAirwall_2)-0.265×(meanDiameterOfAirway_1). The optimal cutoff value for the score was -9.45. The areas under the ROC curve (AUC) for predicting 180 d survival was 0.843 (95%CI: 0.773-0.952) in the training set, 0.778 (95%CI: 0.527-0.999) in the internal test set, and 0.762 (95%CI: 0.615-0.921) in the external test set. The Hosmer-Lemeshow goodness-fit test results showed that the model had a good fitting effect (training set: χ²=8.058, P=0.428; internal validation set: χ²=12.883, P=0.116; internal validation set: χ²=3.141, P=0.925). The decision curve shows that when the risk threshold of the training set is 0 to 79%, that of the internal validation set is 0 to 81%, and that of the independent validation set is 0 to 82%, the prediction model has a clinical net benefit. In the three data sets, the 180 d PFS rate of the high-risk group (QCT score ≥ -9.45) was lower than that of the low-risk group (QCT score < -9.45) (training set: 5.1% vs 66.7%; internal validation set: 180 d progression-free survival rate 12.5% vs 75%; external validation set: 180 d progression-free survival rate 68.6% vs 100.0%, all P<0.05). Conclusion: Based on the QCT image features, a prognostic prediction model for chemotherapy combined with immunotherapy in LUSC was constructed, providing an effective means for predicting the response of chemotherapy combined with immunotherapy in LUSC patients.

PMID:41320660 | DOI:10.3760/cma.j.cn112137-20250619-01495

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4048-4055. doi: 10.3760/cma.j.cn112137-20250924-02479.

ABSTRACT

Objective: To analyze the mutational landscape of primary and acquired mesenchymal to epithelial transition factor (MET) mutations in non-small cell lung cancer (NSCLC) and investigate the impact of co-mutations on the therapeutic efficacy. Methods: A total of 316 pathologically confirmed NSCLC patients with MET gene mutations treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Shanghai Chest Hospital, Shanghai Jiao Tong University, between January 2012 and May 2023 were retrospectively enrolled. Demographics, clinicopathological characteristics, and treatment outcomes were collected. Patients were classified into primary MET mutation and acquired MET mutation groups according to the timing of mutation occurrence, and intergroup differences were compared. Treatment responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. Follow-up data on efficacy and progression-free survival (PFS) were collected through telephone calls and medical record review. The follow-up continued until January 2024. Kaplan-Meier survival curves were generated, and log-rank tests were used to compare PFS between patients with different co-mutations receiving tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapy. Results: Compared to the acquired mutation group, patients with primary MET mutations were significantly older[median (Q₁, Q₃) age: 65 (58, 71) vs 59 (51, 64) years; P<0.001], had a higher proportion of males [62.4% (141/226) vs 48.9% (44/90), P=0.028] and a higher proportion of never-smokers [48.7% (110/226) vs 30% (27/90), P=0.002]. In the primary mutation group, TP53 was the most common co-mutation gene (43%, 51/118), followed by EGFR (32%, 38/118) and KRAS (9%, 11/118). In the acquired mutation group, 89% (69/73) of patients retained the EGFR mutation. Aside from EGFR, the most common co-mutation genes were TP53 (63%, 46/73) and CDK4 (12%, 9/73). Among the 62 patients treated with MET-TKI, those with concurrent EGFR-sensitive mutations had a median PFS of 3.1 (95%CI: 2.4-7.2) months, significantly shorter than that of EGFR wild-type patients [18.2 (95%CI: 9.2-22.1) months, P<0.001]. Patients with TP53 co-mutations had a median PFS of 7.5 (95%CI: 6.4-not reached) months, which was significantly longer than TP53 wild-type patients [3.4 (95%CI: 1.8-4.3) months, P=0.035]. Among the 57 patients treated with ICI, those with EGFR-sensitive mutations had a median PFS of 5.3 (95%CI: 2.0-8.2) months, which was significantly shorter than EGFR wild-type patients [10.4 (95%CI: 5.2-not reached) months, P=0.027]. Patients with TP53 co-mutations had a median PFS of 5.9 (95%CI: 3.8-20.4) months, which was longer than TP53 wild-type patients [3.0 (95%CI: 2.0-4.5) months], although the difference was not statistically significant (P=0.344). Conclusions: Primary and acquired MET mutations in NSCLC exhibit distinct genomic characteristics. Patients harboring concurrent EGFR mutations in NSCLC may derive less benefit from MET-TKI and ICI, whereas those harboring TP53 co-mutations tend to experience more favorable outcomes compared with TP53 wild-type NSCLC patients when treated with MET-TKI.

PMID:41320659 | DOI:10.3760/cma.j.cn112137-20250924-02479

Zhonghua Yi Xue Za Zhi. 2025 Dec 2;105(44):4041-4047. doi: 10.3760/cma.j.cn112137-20250405-00836.

ABSTRACT

Objective: To explore the effectiveness and safety of anlotinib combination regimens in patients with previously immunotherapy treated advanced non-small cell lung cancer (NSCLC). Methods: This study retrospectively included 85 patients with previously immunotherapy treated advanced NSCLC who received anlotinib combination regimens or single-agent chemotherapy in the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023. The observation group was consisted of 43 patients who received anlotinib combination regimens, and the control group was consisted of 42 patients who received single-agent chemotherapy. Observation group received anlotinib combined with chemotherapy and anlotinib combined with immunotherapy, while control group received single-agent chemotherapy. The follow-up period ended on May 25, 2024. The baseline characteristics, recent effectiveness, prognosis, and adverse reactions were compared between the observation group and the control group. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences. Results: In observation group, there were 29 males and 14 females with a median age [M (Q₁, Q₃)] of 63 (27, 73) years; in control group, there were 27 males and 15 females, with a median age of 64 (28, 73) years. Objective response rates for the observation group and control group were 23.3% (10/43) and 14.3% (6/42), respectively, with no statistically significant difference (P=0.290). Disease control rates were 83.7% (36/43) and 57.1% (24/42) for the observation and the control groups, respectively, with a statistically significant difference (P=0.007). The median follow-up duration for the observation group and the control group was 14.2 and 9.6 months, respectively. Prognosis results indicated that the median PFS for the observation group and the control group were 6.1 (95%CI: 2.41-9.79) and 2.9 months (95%CI: 2.59-3.21), respectively. The observation group was significantly higher than the control group (P=0.009). The median OS were 15.5 (95%CI: 8.99-22.01) and 10.3 months (95%CI: 7.87-12.74), respectively. The observation group was also significantly higher than the control group (P=0.016). Safety analysis results exhibited that the incidence of adverse reactions of different grades in the observation group and control groups were 88.4% (38/43) and 81.0% (34/42), respectively; The grade ≥3 adverse reactions occurred in 41.9% (18/43) and 33.3% (14/42), respectively, with no statistically significant difference (both P>0.05). The grade≥3 adverse reactions were controlled through dose adjustment and symptomatic treatment. Conclusion: In patients with previously immunotherapy treated advanced NSCLC, anlotinib combination regimens demonstrates preliminary efficacy and tolerable safety profile compared to single-agent chemotherapy.

PMID:41320658 | DOI:10.3760/cma.j.cn112137-20250405-00836

Tissue Barriers. 2025 Nov 30:2585246. doi: 10.1080/21688370.2025.2585246. Online ahead of print.

ABSTRACT

The placenta possesses several structural and immunological barriers against viral infections, the SARS-CoV-2 detection in placental tissues has raised concerns regarding possible alternative viral entry mechanisms beyond the canonical ACE2/TMPRSS2-mediated pathway. In this context, the present study evaluated the immunohistochemical expression patterns of ADAM17, Cathepsin L, Clathrin, ACE-2, Furin, NRP-1, and TMPRSS2-molecules involved in SARS-CoV-2 placental entry pathways – as well as the detection of viral RNA by RT-qPCR in paraffin-embedded samples. The study included 75 paraffin-embedded placental samples (decidua and villi) collected after spontaneous placental delivery at birth from patients who tested positive for COVID-19 (COVID-19 Group), and 19 paraffin-embedded control placental samples collected prior to the COVID-19 pandemic (NON-COVID-19 Group). A statistically significant reduction in NRP-1 expression was observed in the COVID-19 group decidua (p < 0.001), including in RT-qPCR – positive samples (p = 0.001), regardless of comorbidities or underlying conditions. A statistically significant reduction in Clathrin expression was also found in the decidual samples of the COVID-19 group and in RT-qPCR – positive samples (p = 0.05and 0.013, respectively), while Cathepsin L expression was significantly increased in the placental villi of the COVID-19 group (p < 0.001) and in RT-qPCR – positive samples (p = 0.005). These findings may contribute to a better understanding of the mechanisms underlying SARS-CoV-2 interaction with the placenta, possibly through auxiliary and/or endocytic entry pathways, and may support future investigations into the impact of these alterations in the context of maternal SARS-CoV-2 infection.

PMID:41319265 | DOI:10.1080/21688370.2025.2585246

Endocrinol Diabetes Metab. 2026 Jan;9(1):e70129. doi: 10.1002/edm2.70129.

ABSTRACT

OBJECTIVE: Postoperative hypocalcemia and hypoparathyroidism are common complications after thyroidectomy, often impairing quality of life (QoL). This study investigates the impact of preoperative calcium and magnesium supplementation on postoperative QoL and hypocalcemia in patients undergoing total thyroidectomy for symptomatic nodular goitre or Graves’ disease.

METHODS: A total of 62 patients undergoing thyroidectomy for benign thyroid diseases were randomised into two groups. The intervention group (IG, n = 31) received 500 mg calcium carbonate thrice daily and 300 mg magnesium carbonate once daily for 2 weeks preoperatively, while the control group (CG, n = 31) received no supplementation. Laboratory parameters (Ca, Mg, PTH, 25-OH-Vitamin D) were measured at study enrolment (T₁), preoperatively (T₂), immediately postoperatively (T₃) and 6 weeks post-discharge (T₄). QoL was assessed using EQ-5D and ThyPro39de questionnaires.

RESULTS: QoL significantly improved postoperatively in both groups. Patients with Graves’ disease in the IG reported earlier QoL improvements immediately post-surgery (T₃). Postoperative hypocalcemia occurred in 19.4% of IG patients and 25% of CG patients, with hypoparathyroidism in 16% and 23%, respectively. The IG demonstrated higher postoperative calcium levels and fewer hypocalcemia symptoms, especially in Graves’ disease patients (not significant). Vitamin D deficiency was prevalent (66.7%) but showed no correlation with hypocalcemia.

DISCUSSION: Preoperative calcium and magnesium supplementation might have positive effects on postoperative QoL, especially in Graves’ disease patients, and may reduce hypocalcemia symptoms. This simple, inexpensive and low-risk intervention may be beneficial in the preoperative setting prior to thyroidectomy. Although the observed effect did not reach statistical significance, it could still be of clinical relevance. The additional benefit of preoperative magnesium supplementation seems to be of minor significance, while the effect of pre-existing vitamin D deficiency remains uncertain.

PMID:41319240 | DOI:10.1002/edm2.70129

Clin Transl Sci. 2025 Dec;18(12):e70412. doi: 10.1111/cts.70412.

ABSTRACT

Proteomics can identify pharmacodynamic (PD) biomarkers by detecting protein changes in response to drug treatment, providing insights into drug mechanism and biological effects. In this study, we profiled over 7000 plasma proteins to identify potential PD biomarkers for the interleukin-5 (IL-5) inhibitors mepolizumab and reslizumab, which are approved for treating eosinophilic asthma. We used longitudinal plasma samples from healthy participants treated with a single dose of mepolizumab (n = 8, 24 mg) or reslizumab (n = 8, 0.8 mg/kg), or placebo (n = 8) to identify differentially expressed proteins. We then characterized PD biomarker candidates by their magnitude of response, area under the effect curve (AUEC), dose-response, variability, and replication of response at a lower dose for mepolizumab (n = 8, 12 mg) or reslizumab (n = 8, 0.4 mg/kg) compared to placebo. Eosinophil major basic protein (EMBP) and proteoglycan-3 (PRG3) were differentially expressed in response to mepolizumab and reslizumab, respectively, achieving Bonferroni-adjusted statistical significance (p-value < 6.86E-06) and nominal significance (p-value < 5.0E-05) with the other IL-5 inhibitor. EMBP showed a > 20% fold change difference with mepolizumab (24 mg) versus placebo at peak time, and PRG3 demonstrated a > 20% fold change with reslizumab (0.8 mg/kg) versus placebo at peak time. Both proteins had significant AUEC with both drug doses, with EMBP AUEC only significant (absolute AUEC high > low dose) at the higher mepolizumab dose. Both biomarkers showed dose-response trends and comparable variability to placebo. Our study identified EMBP and PRG3 as promising plasma PD biomarkers for IL-5 inhibitors, warranting further validation for early phase trials and biosimilar development programs.

PMID:41319239 | DOI:10.1111/cts.70412

J Diabetes Investig. 2025 Nov 30. doi: 10.1111/jdi.70205. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyperglycemia or diabetes mellitus (DM) is a well-known risk factor for pancreatic cancer, but it is uncertain whether well-controlled glycemic status can affect the pancreatic cancer incidence rate.

METHODS: This study used 2,993,519 individuals who underwent four consecutive national annual health screenings between 2009 and 2013. The study participants were divided into three groups: nondiabetes mellitus (non-DM), new-onset DM, and known DM. Each group was further subcategorized based on the fasting blood glucose (FBG) levels and use of antidiabetic medication: well-controlled (<100 mg/dL), moderately controlled (100-125), or poorly controlled (>126).

RESULTS: During a median follow-up of 6.3 years, the incidence rate of pancreatic cancer in the non-DM group significantly increased in the moderately controlled group compared with that in the well-controlled group, regardless of whether the FBG level was recently or initially elevated. However, no dose-response relationship was observed between glucose control status and pancreatic cancer incidence, although the incidence of pancreatic cancer in the new DM and known DM groups was generally higher than that in the non-DM group.

CONCLUSION: The pancreatic cancer incidence rate in the non-DM group significantly increased in the poorly controlled group. These findings suggest that in populations without DM, maintaining optimal glucose control may be associated with a lower risk of developing pancreatic cancer.

PMID:41319229 | DOI:10.1111/jdi.70205