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Heat stress poses a significant environmental challenge that profoundly impacts wheat productivity. It disrupts vital physiological processes such as photosynthesis, by impeding the functionality of the photosynthetic apparatus and compromising plasma membrane stability, thereby detrimentally affecting grain development in wheat. The scarcity of identified marker trait associations pertinent to thermotolerance presents a formidable obstacle in the development of marker-assisted selection strategies against heat stress. To address this, wheat accessions were systematically exposed to both normal and heat stress conditions and phenotypic data were collected on physiological traits including proline content, canopy temperature depression, cell membrane injury, photosynthetic rate, transpiration rate (at vegetative and reproductive stage and 'stay-green'. Principal component analysis elucidated the most significant contributors being proline content, transpiration rate, and canopy temperature depression, which exhibited a synergistic relationship with grain yield. Remarkably, cluster analysis delineated the wheat accessions into four discrete groups based on physiological attributes. Moreover, to explore the relationship between physiological traits and DNA markers, 158 wheat accessions were genotyped with 186 SSRs. Allelic frequency and polymorphic information content value were found to be highest on genome A (4.94 and 0.688), chromosome 1A (5.00 and 0.712), and marker Xgwm44 (13.0 and 0.916). Population structure, principal coordinate analysis and cluster analysis also partitioned the wheat accessions into four subpopulations based on genotypic data, highlighting their genetic homogeneity. Population diversity and presence of linkage disequilibrium established the suitability of population for association mapping. Additionally, linkage disequilibrium decay was most pronounced within a 15-20 cM region on chromosome 1A. Association mapping revealed highly significant marker trait associations at Bonferroni correction P < 0.00027. Markers Xwmc418 (located on chromosome 3D) and Xgwm233 (chromosome 7A) demonstrated associations with transpiration rate, while marker Xgwm494 (chromosome 3A) exhibited an association with photosynthetic rates at both vegetative and reproductive stages under heat stress conditions. Additionally, markers Xwmc201 (chromosome 6A) and Xcfa2129 (chromosome 1A) displayed robust associations with canopy temperature depression, while markers Xbarc163 (chromosome 4B) and Xbarc49 (chromosome 5A) were strongly associated with cell membrane injury at both stages. Notably, marker Xbarc49 (chromosome 5A) exhibited a significant association with the 'stay-green' trait under heat stress conditions. These results offers the potential utility in marker-assisted selection, gene pyramiding and genomic selection models to predict performance of wheat accession under heat stress conditions., (© 2024. The Author(s).)

Objective: General surgery trainees interested in performing hepatopancreatobiliary (HPB) surgery can choose from multiple fellowship pathways, namely HPB, surgical oncology (SO), and abdominal transplant-HPB (TXP-HPB). Although focused on similar operations, each program offers distinct clinical and technical emphases., Design: An annual inter-institutional exchange between TXP-HPB and SO fellowships, starting in 2014., Setting and Participants: TXP-HPB fellows from Washington University in St. Louis (WUSTL) and SO fellows from Memorial Sloan Kettering Cancer Center (MSKCC)., Results: About 14 fellows have participated in the exchange so far, 13 of whom responded to our survey. At MSKCC, TXP-HPB fellows performed a median of 24 cases, including 6 major pancreatic resections, 3 major hepatectomies, 4 hepatic artery infusion pump insertions, and 1 major biliary case. At WUSTL, SO fellows performed a median of 16 cases, including 5 liver transplants, 2 major pancreatic resections, 2 major hepatectomies, and 2 major biliary cases. About 92.3% of respondents stated they would repeat the rotation, with SO fellows emphasizing the exposure to vascular anastomoses and transplant-HPB fellows appreciating the oncologic focus., Conclusions: A monthlong inter-institutional exchange offers a unique opportunity to standardize and improve HPB education., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Robotic donor nephrectomy (RDN) has emerged as a safe alternative to laparoscopic donor nephrectomy (LDN). Having previously demonstrated comparable efficacy, this study aims to examine postoperative analgesia use (opioid and non-opioid) in the two groups., Methods: We conducted a retrospective review of 300 living donor nephrectomies performed at our center, comparing 150 RDN's with a contemporary cohort of 150 hand-assisted LDN's. In addition to clinical and demographic information, data on postoperative inpatient opioid and non-opioid analgesia (from patient's arrival to the surgical floor after surgery till the time of discharge) was collected. Opioid dosages were standardized by conversion to morphine milligram equivalents (MME). All patients were managed post-operatively under a standardized ERAS pathway for living donor nephrectomy patients., Results: There were no significant differences in donor age, gender, and BMI between RDN and LDN groups. Total post-operative opioid use (MME's) was significantly lower in RDN patients (RDN 27.1 vs. LDN 46.3; P < 0.0001). Breakdown of opioid use with post-operative (POD) day demonstrated significantly lower use in RDN group on POD1 (RDN 8.6 vs. LDN 17.0; P < 0.05), and POD2 (RDN 3.9 vs LDN 10; P < 0.05). RDN patients had a shorter post-operative length of stay (LOS) (RDN 1.69 days vs. LDN 1.98; P = 0.0003). There were no differences between groups in non-opioid medication use, complications, and readmission rates., Conclusion: RDN has comparable safety to hand-assist LDN and offers additional benefits of lower postoperative opioid requirement and a shorter hospital LOS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of ≥VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow-up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Background: Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH., Methods: We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598., Results: A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% ( n  = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB ( N  = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing., Conclusion: Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.

We investigated the use of robotic objective performance metrics (OPM) to predict number of cases to proficiency and independence among abdominal transplant fellows performing robot-assisted donor nephrectomy (RDN). 101 RDNs were performed by 5 transplant fellows from September 2020 to October 2023. OPM included fellow percent active control time (%ACT) and handoff counts (HC). Proficiency was defined as ACT ≥ 80% and HC ≤ 2, and independence as ACT ≥ 99% and HC ≤ 1. Case number was significantly associated with increasing fellow %ACT, with proficiency estimated at 14 cases and independence at 32 cases (R 2  = 0.56, p < 0.001). Similarly, case number was significantly associated with decreasing HC, with proficiency at 18 cases and independence at 33 cases (R 2  = 0.29, p < 0.001). Case number was not associated with total active console time (p = 0.91). Patient demographics, operative characteristics, and outcomes were not associated with OPM, except for donor estimated blood loss (EBL), which positively correlated with HC. Abdominal transplant fellows demonstrated proficiency at 14-18 cases and independence at 32-33 cases. Total active console time remained unchanged, suggesting that increasing fellow autonomy does not impede operative efficiency. These findings may serve as a benchmark for training abdominal transplant surgery fellows independently and safely in RDN., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Hypertrophic cardiomyopathy (HCM) is a dominantly inherited disease associated with sudden immune cell associations that remain unclear. The aim of this study was to comprehensively screen candidate markers associated with HCM and immune cells and explore potential pathogenic pathways., Methods: First, download the GSE32453 dataset to identify differentially expressed genes (DEGs) and perform Gene Ontology and pathway enrichment analysis using DAVID and GSEA. Next, construct protein-protein interaction (PPI) networks using String and Cytoscape to identify hub genes. Afterward, use CIBERSORT to determine the proportion of immune cells attributed to key genes in HCM and conduct ROC analysis based on the external dataset GSE36961 to evaluate their diagnostic value. Finally, validate the expression of key genes in the hypertrophic cardiomyocyte model through qRT-PCR using data from the HPA database., Results: Comprehensive analysis revealed that there were 254 upregulated genes and 181 downregulated genes in HCM. The enrichment study underscored pathways of inflammatory signaling, including MAPK and PI3K-Akt pathways. Pathways abundant in genes associated with HCM encompassed myocardial contraction and NADH dehydrogenase activity. Additionally, the analysis of immune infiltration revealed a notable increase in macrophages, NK cells, and monocytes in the HCM group, showing statistically significant variances in CD4 memory resting T cell infiltration when compared to the healthy control group. Within the validation dataset GSE36961, the Area Under the Curve (AUC) scores for eight crucial genes (FOS, CD86, CD68, BDNF, PIK3R1, PLEK, RAC2, CCL2) each exceeded 0.8. The HPA database revealed the positioning traits and paths of these eight crucial genes in smooth muscle cells, myocardial cells, and fibroblasts. The outcomes of the qRT-PCR were aligned with the sequencing findings., Conclusion: Bioinformatics analysis unveiled pivotal genes, pathways, and immune involvement, illuminating the molecular underpinnings of HCM. These findings suggest promising therapeutic targets for clinical applications., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gong et al.)

Giant bladder stones, defined as stones weighing over 100 g and/or measuring more than 4 cm in diameter, are relatively uncommon compared to other types of urinary tract stones. This patient, an 85-year-old male with an unknown medical history, initially presented with urinary incontinence and hematuria. Radiological findings revealed a large prostate, a forgotten left renal double-J (DJ) stent for more than 20 years with an encrusted bladder stone, and additional calculi in the lower pole of the left kidney. The patient underwent laser cystolithotripsy, but due to the complexity of the case, a second procedure was scheduled. Following the second procedure, the patient experienced a generalized tonic-clonic seizure and subsequent loss of consciousness, which was attributed to hyponatremia. The patient received appropriate management to correct hyponatremia and antiepileptic medication to control the seizure. The patient's condition eventually improved and he was discharged home with prescribed medications and follow-up appointments. This case emphasizes the potential complications of giant bladder stones and a forgotten DJ stent in an 85-year-old male patient as a rare consequence following such a rare presentation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Khushaym et al.)

Background: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM., Design and Methods: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM., Results: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m 2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes., Conclusion: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes.

Water bodies are highly pollution-prone areas in which mercury (Hg) is considered as a major menace to aquatic organisms. However, the information about the toxicity of mercuric chloride (HgCl 2 ) in a vital organ such as the liver of fish is still inadequate. This study aimed to assess the impact of mercuric chloride (HgCl 2 ) exposure on the liver of Channa punctata fish over 15, 30, and 45 days, at two different concentrations (0.039 mg/L and 0.078 mg/L). Mercury is known to be a significant threat to aquatic life, and yet, information regarding its effects on fish liver remains limited. The results of this study demonstrate that exposure to HgCl 2 significantly increases oxidative stress markers, such as lipid peroxidation (LPO) and protein carbonyls (PC), as well as the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in the fish. Additionally, the transcriptional and protein analysis of specific genes and molecules associated with necroptosis and inflammation, such as ABCG2, TNF α, Caspase 3, RIPK 3, IL-1β, Caspase-1, IL-18, and RIPK1, confirm the occurrence of necroptosis and inflammation in the liver. Histopathological and ultrastructural examinations of the liver tissue further reveal a significant presence of liver steatosis. Interestingly, the upregulation of PPARα suggests that the fish's body is actively responding to counteract the effects of liver steatosis. This study provides a comprehensive analysis of oxidative stress, biochemical changes, gene expression, protein profiles, and histological findings in the liver tissue of fish exposed to mercury pollution in freshwater environments., (© 2024. The Author(s).)

Purpose: The objective of our study was to assess awareness, attitudes, and practices regarding artificial intelligence (AI) among healthcare workers in private polyclinics in Jeddah, Saudi Arabia., Methods: We conducted cross-sectional study among healthcare workers in private clinics in Jeddah. Data was collected using a structured, validated questionnaire in Arabic and English on awareness, attitudes, and behaviors regarding AI. Cronbach's alpha for the questionnaire ranged from 0.6 to 0.8. Descriptive and bivariate analysis was done to assess the scores and their association of various sociodemographic variables with awareness, attitudes, and behaviors regarding AI. Multiple linear regression was performed to predict the scores of awareness, attitudes, and behaviors based on the sociodemographic variables., Results: We recruited 361 participants for this study. Approximately, 62% of the healthcare workers were female. The majority (36%) of healthcare workers were nurses, while 25% were physicians. The median awareness, attitude, and behavioral scores were 5/6 (IQR 3-6), 5/8 (IQR 4-7), and 0/3 (IQR 0), respectively. Approximately three-fourths (74%) of the healthcare workers believed that they understood the basic computational principles of AI. Only half of the participants were willing to use AI when making future medical decisions. We found that male healthcare workers had better knowledge scores regarding AI as compared to female healthcare workers (Beta = 0.555, 95%, p value = 0.010), while for attitude scores, being administrative employee as compared to other employees was found to have negative attitude towards AI (Beta = 0.049, 95%, p value = 0.03)., Conclusion: We found that healthcare workers had an overall good awareness and optimistic attitude toward AI. Despite this, the majority is worried about the potential consequences of replacing their jobs with AI in the future. There is a dire need to educate and sensitize healthcare workers regarding the potential impact of AI on healthcare., Competing Interests: The authors report that there is no conflict of interest., (© 2024 Serbaya et al.)

Background: Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT) has not been fully elucidated., Methods: UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables., Results: A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit (ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001) compared to recipients of younger donor (YD) grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1) from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable., Conclusion: Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

DNA binding proteins with one finger (Dof ) transcription factors are essential for seed development and defence against various biotic and abiotic stresses in plants. Genomic analysis of Dof has not been determined yet in pitaya (Selenicereus undatus ). In this study, we have identified 26 Dof gene family members, renamed as HuDof-1 to HuDof-26 , and clustered them into seven subfamilies based on conserved motifs, domains, and phylogenetic analysis. The gene pairs of Dof family members were duplicated by segmental duplications that faced purifying selection, as indicated by the K a /K s ratio values. Promoter regions of HuDof genes contain many cis -acting elements related to phytohormones including abscisic acid, jasmonic acid, gibberellin, temperature, and light. We exposed pitaya plants to different environmental stresses and examined melatonin's influence on Dof gene expression levels. Signifcant expression of HuDof -2 and HuDof -6 were observed in different developmental stages of flower buds, flowers, pericarp, and pulp. Pitaya plants were subjected to abiotic stresses, and transcriptome analysis was carried out to identify the role of Dof gene family members. RNA-sequencing data and reverse transcription quantitative PCR-based expression analysis revealed three putative candidate genes (HuDof -1, HuDof -2, and HuDof -8), which might have diverse roles against the abiotic stresses. Our study provides a theoretical foundation for functional analysis through traditional and modern biotechnological tools for pitaya trait improvement.

The present study explores growth potential of two medicinal herbs, Withania somnifera (Ashwagandha or 'A') and Asparagus racemosus (Shatavari or 'S') after their dietary inclusion in fish, Channa punctatus (13.5 ± 2 g; 11.5 ± 1 cm). Three hundred well-acclimatized fish were distributed into 10 groups- C (Control), S1 (1% S), S2 (2% S), S3 (3% S), A1 (1% A), A2 (2% A), A3 (3% A), AS1 (1% A and S), AS2 (2% A and S), and AS3 (3% A and S), each having 10 specimens. Fish were fed with these diets for 60 days. The study was performed in triplicate. Growth indices- weight gain (WG), specific growth rate percentage (SGR%), feed intake (FI), and condition factor (CF), after 30 and 60 days, were found significantly (p < 0.05) up-regulated in all the groups, except S1, when compared to the C. A significant (p < 0.05) increase in final body weight (FBW) was noticed in all the groups, except S1, after 60 days. Relative to the control group, activities of lipase and amylase in the gut tissue were elevated in all groups, at both sampling times, with the exception of lipase in S1 at 60 days, and amylase in S1 at day 30 and day 60 and S2 at day 60. The mRNA expression of myogenic regulatory factors (MRFs) was also found to be significantly (p < 0.05) up-regulated with the highest fold changes recorded in AS3 for myoD (3.93 ± 0.91); myoG (6.71 ± 0.30); myf5 (4.40 ± 0.33); MRF4 (4.94 ± 0.21) in comparison to the C., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32-77). The disease control rate was 100% in patients with PDL1 ≥ 1% ( n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4-21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy.

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM., (© 2024. The Author(s).)

Background: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment., Case Presentation: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m 2 ). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications., Conclusions: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia., Competing Interests: No one of the authors received payment for this work. The fund provided by Recordati Rare Diseases was used only to cover medical writing and editorial assistance by Guy Ramsay., (© 2024 Baagar, Sadiq, Khan, Dabbous, Rohani, Licensee HBKU Press.)

Purpose: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar., Methods: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015-2020) among patients with new-onset T1D (NT1D) in Qatar., Results: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11-15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11-23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 10 3 /uL) at admission compared to classic T1D (10.6 × 10 3 /uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group., Conclusion: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D., (© 2024. The Author(s).)

Background: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation-induced joint damage, which can cause lasting disability. Therefore, early diagnosis and treatment of RA are crucial. Herein, we evaluated whether exosomal microRNAs (miRNAs) could be served as promising biomarkers that can accelerate the diagnosis of RA and development of therapies for RA., Methods: First, we performed small RNA sequencing to determine the miRNA profiles of serum exosomes within a screening cohort comprised of 18 untreated active RA patients, along with 18 age and gender-matched healthy controls (HCs). Subsequently, the miRNA profiles were then validated in a training cohort consisting of 24 RA patients and 24 HCs by RT-qPCR. Finally, the selected exosomal miRNAs were validated in a larger cohort comprising 108 RA patients and 103 HCs. The diagnostic efficacy of the exosomal miRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Biological functions of the miRNAs were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses., Results: Our results first demonstrated a noteworthy upregulation of three candidate miRNAs (miR-885-5p, miR-6894-3p, and miR-1268a) in the RA patients' serum exosomes compared to HCs. The combination of three miRNAs along with anti- citrullinated peptide antibodies (ACPA) exhibited excellent diagnostic accuracy, yielding an area under the curve (AUC) of 0.963 (95 % CI : 0.941-0.984), sensitivity of 87.96 %, and specificity of 93.20 %. Notably, miR-885-5p exhibited remarkable discriminatory capacity by itself in indistinguishing ACPA- negative RA patients from HCs, with an AUC of 0.993 (95 % CI : 0.978-1.000), sensitivity of 96.67 %, and specificity of 100 %. Moreover, the expression of miR-1268a in the assessment of therapeutic effectiveness displayed significant reduction on 29th day of Methotrexate (MTX) treatment in RA patients. This decreased expression paralleled with trends observed in tender 28-joint count (TJC28), swollen 28-joint count (SJC28), and disease activity score with 28-joint count using C-reactive protein (DAS28-CRP), all of which are indicative of RA disease activity. Finally, predictive analysis indicated that, these three exosomal miRNAs target pivotal signaling molecules involved in inflammatory pathways, thereby demonstrating effective modulation of the immune system., Conclusions: In this study, we successfully demonstrated the promising potential for serum exosomal miRNAs, particularly miR-885-5p, miR-6894-3p and miR-1268a as biomarkers for early diagnosis and prediction of RA for the first time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication., Methods: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16., Results: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes., Conclusion: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves' disease (GD) is rare and complicates the management decision., Methods: We present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase., Case Presentation: A 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3-4.2) mIU/L, FT3 19.7 (3.7-6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide., Results: Fourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12-5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6-19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3-64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog., Conclusion: TSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies., (© 2024. The Author(s).)

Introduction: Ultrasensitive bacterial detection methods are crucial to ensuring accurate diagnosis and effective clinical monitoring, given the significant threat bacterial infections pose to human health. The aim of this study is to develop a biosensor with capabilities for broad-spectrum bacterial detection, rapid processing, and cost-effectiveness., Methods: A magnetically-assisted SERS biosensor was designed, employing wheat germ agglutinin (WGA) for broad-spectrum recognition and antibodies for specific capture. Gold nanostars (AuNSs) were sequentially modified with the Raman reporter molecules and WGA, creating a versatile SERS tag with high affinity for a diverse range of bacteria. Staphylococcus aureus ( S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa ) antibody-modified Fe 3 O 4 magnetic gold nanoparticles (MGNPs) served as the capture probes. Target bacteria were captured by MGNPs and combined with SERS tags, forming a "sandwich" composite structure for bacterial detection., Results: AuNSs, with a core size of 65 nm, exhibited excellent storage stability (RSD=5.6%) and demonstrated superior SERS enhancement compared to colloidal gold nanoparticles. Efficient binding of S. aureus and P. aeruginosa to MGNPs resulted in capture efficiencies of 89.13% and 85.31%, respectively. Under optimized conditions, the developed assay achieved a limit of detection (LOD) of 7 CFU/mL for S. aureus and 5 CFU/mL for P. aeruginosa . The bacterial concentration (10-10 6 CFU/mL) showed a strong linear correlation with the SERS intensity at 1331 cm -1 . Additionally, high recoveries (84.8% - 118.0%) and low RSD (6.21% - 11.42%) were observed in spiked human urine samples., Conclusion: This study introduces a simple and innovative magnetically-assisted SERS biosensor for the sensitive and quantitative detection of S. aureus or P. aeruginosa , utilizing WGA and antibodies. The developed biosensor enhances the capabilities of the "sandwich" type SERS biosensor, offering a novel and effective platform for accurate and timely clinical diagnosis of bacterial infections., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Cheng et al.)

Background: The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the predictors of healthcare resource utilization in DKA is limited and inconsistent. This study aimed to identify key predictors of hospital length of stay (LOS), readmission and recurrent DKA episodes., Methods: We undertook a retrospective cross-sectional analysis of all DKA admissions from 2015 to 2021 across four hospitals in Qatar. The primary outcomes were the length of stay (LOS), 90-day readmission and 6-month and 1-year DKA recurrence., Results: We included 922 patients with a median age of 35 years (25-45). 62% were males with type-1 diabetes-mellitus (T1DM) and type-2 DM (T2DM), present in 52% and 48% of patients. The median LOS was 2.6 days (IQR 1.1-4.8), and the median DKA resolution time was 18 h (10.5-29). Male-gender, new-onset DM, higher Charlson Comorbidity Index (CCI), lower haemoglobin, sodium and potassium, higher urea, longer DKA duration and MICU admission predicted a longer LOS in a multivariate regression analysis. None of the factors were significantly associated with 90-day readmission. Patients with pre-existing T1DM were more likely to have a six-month DKA recurrence than pre-existing T2DM. Patients with a 6-month DKA recurrence, female gender and T1DM had higher odds of 12-month recurrence, whereas a consult with a diabetes educator at the index admission was associated with decreased odds of recurrence., Conclusions/interpretation: This is the most extensive study from the Middle-East region reporting on LOS, readmissions and the recurrence of DKA. Results from this study with a diverse population may be valuable for physicians and healthcare systems to decrease the diabetes-related healthcare burden in DKA patients.

Introduction: Overcrowding in the emergency departments (ED) is linked to adverse clinical outcomes, a negative impact on patient safety, patient satisfaction, and physician efficiency. We aimed to design a medical admission prediction scoring system based on readily available clinical data during ED presentation., Methods: In this retrospective cross-sectional study, data on ED presentations and medical admissions were extracted from the Emergency and Internal Medicine departments of a tertiary care facility in Qatar. Primary outcome was medical admission., Results: Of 320299 ED presentations, 218772 were males (68.3%). A total of 11847 (3.7%) medical admissions occurred. Most patients were Asians (53.7%), followed by Arabs (38.7%). Patients who got admitted were older than those who did not (p <0.001). Admitted patients were predominantly males (56.8%), had a higher number of comorbid conditions and a higher frequency of recent discharge (within the last 30 days) (p <0.001). Age > 60 years, female gender, discharge within the last 30 days, and worse vital signs at presentations were independently associated with higher odds of admission (p<0.001). These factors generated the scoring system with a cut-off of >17, area under the curve (AUC) 0.831 (95% CI 0.827-0.836), and a predictive accuracy of 83.3% (95% CI 83.2-83.4). The model had a sensitivity of 69.1% (95% CI 68.2-69.9), specificity was 83.9% (95% CI 83.7-84.0), positive predictive value (PPV) 14.2% (95% CI 13.8-14.4), negative predictive value (NPV) 98.6% (95% CI 98.5-98.7) and positive likelihood ratio (LR+) 4.28% (95% CI 4.27-4.28)., Conclusion: Medical admission prediction scoring system can be reliably applied to the regional population to predict medical admissions and may have better generalizability to other parts of the world owing to the diverse patient population in Qatar., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zahid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]., Background: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death)., Methods: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function., Results: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%)., Conclusions: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors., Competing Interests: C.C., C.M., L.R., and P.F.: are employed by Organox. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Despite considerable interest in robotic surgery, successful incorporation of robotics into transplant programs has been challenging. Lack of a dedicated OR team with expertise in both robotics and transplant is felt to be a major barrier. This paper assesses the impact of a dedicated robotic transplant team (DART) on program growth and fellowship training at one of the largest robotic transplant programs in North America., Methods: This is a single center, retrospective review of all robotic operations performed on the transplant surgery service from October 2017 to October 2022. DART was incorporated in February 2020 and included transplant first assists (RFAs), scrub technologists and circulating nurses who received robotic training. Robotic experience before and after DART was compared to assess its impact on program growth and training., Results: Four hundred and two robotic cases were performed by five transplant surgeons: 63 pre-DART and 339 post-DART. 40% of cases were transplant-related and 59.5%, HPB. There was a significant increase in case volume (2.5-10.6 cases/month, p < .0001) and complexity (36.5% vs. 70.3% high complexity cases, p < .0001) post-DART. RFA case coverage increased from 17% to 95%, and participation of transplant fellows as primary surgeons increased from 17% to 95% post-DART period (both p < .05). Conversion rates (9.5% vs. 4.1%) and room turn-around-times (TAT) (58.4 vs. 40.3 min) were lower post-DART (p < .05). There were no emergent conversions, conversions in transplant patients, or robot-related complications in either group., Conclusion: OR teams with expertise in robotics and transplant surgery can accelerate growth of robotic transplant programs while maintaining patient safety., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Antithyroid drugs (ATDs) are the cornerstone of hyperthyroidism management. Hepatotoxicity due to ATDs can range from mild transaminase elevation to liver transplantation requirement and mortality., Objective: The primary objective of the systematic review was to assess the clinical characteristics and outcomes of patients with drug induced liver injury (DILI) due to ATDs., Methods: We conducted a systematic review of PUBMED, SCOPUS, and EMBASE on characteristics and outcomes of adults (>18 years) with DILI due to ATDs. We defined DILI as bilirubin ≥2.5 mg/dL or international normalized ratio >1.5 with any rise in alanine aminotransferase (ALT), aminotransferase (AST), or alkaline phosphatase (ALP), or an elevation of ALT or AST >5 times or ALP >2 times the upper limit of normal without jaundice/coagulopathy., Results: The review included 100 articles describing 271 patients; 148 (70.8%) were female (N = 209). Mean age was 42.9 ± 17.2 years. Graves' disease was the most common indication for ATDs. Carbimazole/methimazole (CBM/MMI) was the most common offending agent (55.7%). DILI pattern was hepatocellular in 41.8%, cholestatic in 41.3%, and mixed in 16.9%. Outcomes included death in 11.8%, liver transplantation in 6.4%, partial improvement in 2.2%, and complete resolution in 79.6% with a median time (IQR) to resolution of 45 (20-90) days. Patients in the propylthiouracil (PTU) group had higher initial bilirubin, initial AST, initial ALT, peak ALT, peak AST, severe and fatal DILI, liver transplantation, and mortality than CBM/MMI. Rechallenge of antithyroid medication was infrequently reported (n = 16) but was successful in 75%., Conclusion: DILI due to ATDs can present with different patterns and should prompt immediate drug discontinuation. Referral to a hepatologist should be considered if severe as transplantation is sometimes required. PTU-induced DILI may have worse outcomes than CBM/MMI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Liver transplant (LT) is the only definitive treatment for end-stage liver disease (ESLD). This review aims to explore current global LT practices, with an emphasis on challenges and disparities that limit access to LT in different regions of the world., Methods: A detailed analysis was performed of present-day liver transplant practices throughout the world, including the etiology of liver disease, patient access to transplantation, surgical costs, and ongoing ethical concerns., Results: Annually, only 10% of the patients needing a liver transplant receive an organ. Currently, the USA performs the highest volume of liver transplants worldwide, followed by China and Brazil. In both North America and Europe, nonalcoholic fatty liver disease is becoming the most common indication for LT, compared to hepatitis B and C in most Asian, South American, and African countries. While deceased donor liver transplant remains the most performed type of LT, living donor liver transplant is becoming increasingly popular in some parts of the world where it is often the only option due to a lack of well-developed infrastructure for deceased organ donation. Ethical concerns in liver transplantation fundamentally revolve around the definition of a deceased donor and the exploitation of living donor liver donation systems., Conclusion: Globally, liver transplant practices and outcomes are varied, with differences driven by healthcare policies, inequities in healthcare access, and ethical concerns., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Matrix metalloproteinase-9 (MMP-9) has been implicated in various tumor cell invasions and metastases. In light of the limitations of traditional methods for MMP-9 detection, we have constructed a novel biosensor depending on cucurbit[8]uril (CB[8]) -mediated host-guest interactions and a sacrificial iron metal-organic framework (FeMOF). Herein, MMP9-specific peptides modified on the gold bare electrode are bonded to the FeMOF@AuNPs@peptide complex through CB[8] addition. The connection between MMP9-specific peptides and signal peptides via CB[8] provides stability as well as enables the immobilization of FeMOF on the electrode surface. When Fe 3+ from the FeMOF interacts with electrochemical buffer K 4 Fe(CN) 6 , Prussian blue will be generated on the gold electrode surface, and a significantly enlarged current response can be detected. However, in the presence of MMP-9, their peptide substrates are specifically cleaved at the site between serine (S) and Leucine (L), which causes an abrupt decrease in the electrochemical signal. The change of signal can reflect MMP-9 concentration. This sensor can reach an ultrahigh sensitivity with a wide detection range of 0.5 pg⋅mL -1 to 500 ng⋅mL -1 and a low detection limit of 1.30 pg⋅mL -1 . Importantly, this sensor is very simple, relying solely on self-sacrificial label of FeMOF, rather than complex functional materials. Additionally, it has been well used in serum samples, showing attractive potential for practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The 2022 incoming fellows' expectations for their robotics training, as well as their perceptions of the utility of the surgical robot, are not well defined., Methods: Cross-sectional survey of 24 AHPBA fellows in 2022, analyzed with descriptive statistics and Spearman's rho., Results: Of 33 current AHPBA fellows, 22 completed the survey (66.7%). Study participants had limited-to-moderate experience with robotics prior to fellowship (mean 2.5 ± SD 1.1; range 1-4). Most participants agreed that robotics influenced their fellowship choice (mean 4.14 ± SD 0.87; range 1-5), would make then more marketable (mean 4.77 ± SD 0.52; range 1-5) and improve job prospects (mean 4.68 ± SD 0.87; range 1-5). Of the study participants, 55% responded that robotics training is "essential" in fellowship, while 64% responded that it is "essential" for their careers. Fellows were only slightly satisfied with overall robotics training within their respective programs (mean 3.44 ± SD 1.17; range 1-5) The majority (73.7%) expect that robotics will comprise <25% of their training. Notably, the majority (75%) have no formal robotics training curriculum., Discussion: This survey identifies potential gaps where robotics training could be improved for future incoming AHPBA fellows., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Robotic donor nephrectomy (RDN) has emerged as a safe alternate to laparoscopic donor nephrectomy (LDN), offering improved visualization, instrument dexterity and ergonomics. There is still concern about how to safely transition from LDN to RDN., Methods: We performed a retrospective review of 150 consecutive living donor operations (75 LDN and 75 RDN) at our center, comparing the first 75 RDN's with the last 75 LDN's performed prior to the initiation of the robotic transplant program. Operative times and complications were used as surrogates of efficiency and safety, respectively, to estimate the learning curve with RDN., Results: RDN was associated with a longer total operative time (RDN 182 vs LDN 144 min; P < 0.0001) but a significantly shorter post-operative length of stay (RDN 1.8 vs LDN 2.1 days; P = 0.0213). Donor complications and recipient outcomes were the same between both groups. Learning curve of RDN was estimated to be about 30 cases., Conclusions: RDN is a safe alternate to LDN with acceptable donor morbidity and no negative impact on recipient outcomes even during the early part of the RDN learning curve. Surgeon preferences for the robotic approach compared to traditional laparoscopy will require further scrutiny to improve ergonomics and operative efficiency., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate the toxic effects of lead (Pb) on key metabolic activities essential for proper germination and seedling growth of maize seeds, experiments were carried out with different levels of Pb (0 to 120 mg of Pb L -1 as PbCl 2 ) applied through growth medium to two maize hybrids H-3310S and H-6724. The research findings indicated that growth and metabolic activities were adversely affected by increased Pb contamination in growth medium; however, a slow increase in these parameters was recorded with increasing time from 0 to 120 h. Protease activity decreased with an increase in the level of Pb contamination but increased with time; consequently, a reduction in seed proteins and an increase in total free amino acids were observed with time. Similarly, α-amylase activity decreased with an increase in Pb concentration in growth medium while it increased with increasing time from 0 to 120 h; consequently, reducing and non-reducing sugars increased with time but decreased with exposure to lead. The roots of both maize hybrids had higher Pb contents than those of the shoot, which decreased the uptake of nitrogen, phosphorus, and potassium. All these nutrients are essential for optimal plant growth; therefore, the reduction in growth and biomass of maize seedlings could be due to Pb toxicity that altered metabolic processes, as sugar and amino acids are necessary for the synthesis of metabolic compounds, rapid cell division, and proper functioning of enzymes in the growing embryo, but all were dramatically reduced due to suppression of protease and α-amylase by toxicity of Pb. In general, hybrid H-3310S performed better in Pb-contaminated growth medium than H-6724.

Background: Diabetic ketoacidosis (DKA) was once known to be specific to type-1 diabetes-mellitus (T1D); however, many cases are now seen in patients with type-2 diabetes-mellitus (T2D). Little is known about how this etiology shift affects DKA's outcomes., Methods: We studied consecutive index DKA admissions from January 2015 to March 2021. Descriptive analyses were performed based on pre-existing T1D and T2D (PT1D and PT2D, respectively) and newly diagnosed T1D and T2D (NT1D and NT2D, respectively)., Results: Of the 922 patients, 480 (52%) had T1D, of which 69% had PT1D and 31% NT1D, whereas 442 (48%) had T2D, of which 60% had PT2D and 40% NT2D. The mean age was highest in PT2D (47.6 ± 13.1 years) and lowest in PT1D (27.3 ± 0.5 years) (P < 0.001). Patients in all groups were predominantly male except in the PT1D group (55% females) (P < 0.001). Most patients were Arabic (76% in PT1D, 51.4% in NT1D, 46.6% in PT2D) except for NT2D, which mainly comprised Asians (53%) (P < 0.001). Patients with NT2D had the longest hospital length of stay (LOS) (6.8 ± 11.3 days) (P < 0.001), longest DKA duration (26.6 ± 21.1 h) (P < 0.001), and more intensive-care unit (ICU) admissions (31.2%) (P < 0.001). Patients with PT1D had the shortest LOS (2.5 ± 3.5 days) (P < 0.001), DKA duration (18.9 ± 4.2 h) (P < 0.001), and lowest ICU admissions (16.6%) (P < 0.001)., Conclusions/interpretation: We presented the largest regional data on differences in DKA based on the type and duration of diabetes- mellitus (DM), showing that T2D is becoming an increasing cause of DKA, with worse clinical outcomes (especially newly diagnosed T2D) compared to T1D., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Hepatic artery infusion pump (HAIP) therapy has become increasingly commonplace in the treatment of intrahepatic tumors. When combined with standard chemotherapy, HAIP therapy demonstrates a higher response rate than chemotherapy alone. Biliary sclerosis is observed in up to 22 % of patients, for whom no treatment has been standardized. This report describes orthotopic liver transplantation (OLT) both as a treatment for HAIP-induced cholangiopathy and as a possible definitive oncologic treatment after HAIP-bridging therapy., Methods: A retrospective study reviewed patients who had undergone HAIP placement followed by OLT at the authors' institution. Patient demographics, neoadjuvant treatment, and postoperative outcomes were reviewed., Results: Seven OLTs were performed for patients with prior HAIP placement. The majority were women (n = 6), and the median age was 61 years (range, 44.5-65.5 years). Transplantation was performed for five patients due to biliary complications secondary to HAIP and two patients because of residual tumor after HAIP therapy. All the OLTs had difficult dissections due to adhesions. Because of HAIP-induced damage, atypical arterial anastomoses were required in six patients (2 patients used a recipient common hepatic artery below the gastroduodenal artery takeoff; 2 patients used recipient splenic arterial inflow; 1 patient used the junction of the celiac and splenic arteries; and 1 patient used the celiac cuff). The one patient with standard arterial reconstruction experienced an arterial thrombosis. The graft was salvaged with thrombolysis. Biliary reconstruction was duct-to-duct in five cases and Roux-en-Y in two cases., Conclusions: The OLT procedure is a feasible treatment option for end-stage liver disease after HAIP therapy. Technical considerations include a more challenging dissection and an atypical arterial anastomosis., (© 2023. Society of Surgical Oncology.)

Background: Diabetic ketoacidosis (DKA) is a life-threatening adverse complication of patients with diabetes mellitus (DM). It is postulated that fasting during Ramadan can increase the risk of DKA; however, there are contradicting data in this regard. Furthermore, studies from Western countries have suggested a seasonal variation in the incidence of DKA. This study examines the differences in the number of DKA episodes during Ramadan compared to the rest of the year in patients with type 1 DM (T1D) and type 2 DM (T2D). Besides, we aim to examine the seasonal difference in the incidence of DKA., Methods: We included consecutive index-DKA admissions from 2015 to 2021 and used descriptive statistics to compare the episodes of DKA in Ramadan vs other months and seasons., Results: Of 922 patients, 480 (52%) had T1D, whereas 442 (48%) had T2D. The median age (IQR) was 35 (25-45) years, with the majority being Arab ( N  = 502, 54.4%). There were 94 DKA admissions in six collective Ramadan months, whereas the DKA admissions ranged from 61 to 88 episodes in other months ( p  = .3). The highest DKA admissions were observed in Autumn ( N  = 236) and the lowest in Spring ( N  = 226) with no statistically significant difference ( p  = .4). There were no differences in DKA severity or new-onset diabetes rates when analyzed based on Hiji months, Roman months, or seasons., Conclusions: DKA occurrence is not increased during Ramadan. We found no evidence of seasonal variations in the rates of DKA in the State of Qatar.

Background: Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies., Results: In this study, CEA + sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA + sEVs was determined. It was found that the NPr of CEA + sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA + sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer., Conclusions: This study demonstrates that the dsDPr of CEA + sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis., (© 2023. The Author(s).)

Background: Kidney transplantation remains the best available treatment for end-stage renal disease. However, promoting graft longevity and preventing allosensitization requires strict adherence with a stringent immunosuppression regimen. The COVID-19 pandemic has offered new challenges for kidney transplant patients and many transplant centers are denying transplantation to unvaccinated patients. The aim of this study was to evaluate whether unvaccinated patients had inferior adherence after kidney transplantation along with a reduction in graft survival., Study Design: Patients undergoing a deceased donor kidney transplantation at a single academic medical center from February 2021 to May 2022 were retrospectively reviewed. February 2021 was chosen as the start date for record review because it was 3 months after the first COVID-19 vaccination was authorized for emergency use. Patients were considered to be vaccinated if they received at least 1 dose of any mRNA vaccine by their transplantation date., Results: Of the 301 patients who met study criteria, 234 were vaccinated and 67 were unvaccinated. Cohorts stratified by vaccination status were well matched. Younger age was an independent risk factor for nonvaccination. Interestingly, unvaccinated patients had worse postoperative adherence with a greater average number of missed postoperative clinic visits (p = 0.03) and a strong trend toward missing 3 or more postoperative clinic visits (p = 0.07). Finally, unvaccinated patients had statistically more subtherapeutic tacrolimus troughs (p = 0.01)., Conclusions: Patients not vaccinated against COVID-19 had higher rate of postoperative nonadherence in key areas of immunosuppression monitoring and clinic visit attendance. Providers should be cognizant that an unvaccinated status may be a harbinger for poor adherence; therefore, stricter strategies for patient outreach are critical to ensure graft success in this vulnerable patient population., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Transfer RNA-derived small RNAs (tsRNAs) tRF-LeuCAG-002 (ts3011a RNA) is a novel class of non-coding RNAs biomarker for pancreatic cancer (PC). Reverse transcription polymerase chain reaction (RT-qPCR) has been unfit for community hospitals that are short of specialized equipment or laboratory setups. It has not been reported whether isothermal technology can be used for detection, because the tsRNAs have rich modifications and secondary structures compared with other non-coding RNAs. Herein, we have employed a catalytic hairpin assembly (CHA) circuit and clustered regularly interspaced short palindromic repeats (CRISPR) to develop an isothermal and target-initiated amplification method for detecting ts3011a RNA. In the proposed assay, the presence of target tsRNA triggers the CHA circuit that transforms new DNA duplexes to activate collateral cleavage activity of CRISPR-associated proteins (CRISPR-Cas) 12a, achieving cascade signal amplification. This method showed a low detection limit of 88 aM at 37 °C within 2 h. Moreover, it was demonstrated for the first time that, this method is less likely to produce aerosol contamination than RT-qPCR by simulating aerosol leakage experiments. This method has good consistency with RT-qPCR in the detection of serum samples and showed great potential for PC-specific tsRNAs point-of-care testing (POCT)., Competing Interests: The 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., (Copyright © 2023 Wu, Xu, Hu, Jiang, Fan, Khan, Sun, Di, Gu, Shen and Li.)

Introduction: Despite recent developments in our comprehension of how the gut microbiota and systemic lupus erythematosus (SLE) are related. The mycobiome: which is a small but crucial part of the gut microbiota and is involved in hosts' homeostasis and physiological processes, remained unexplored in SLE., Methods: We profiled the gut fungal mycobiota based on internal transcribed spacer region 1 (ITS1) sequencing for the gut microbial DNA from the SLE individuals with lupus nephritis (LN) ( n = 23), SLE without LN ( n = 26) and healthy controls ( n = 14) enrolled in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School., Results: The ITS sequencing generated a total of 4.63 million valid tags which were stratified into 4,488 operational taxonomic units (OTUs) and identified about 13 phyla and 262 genera. Patients with SLE were characterized with unique fungal flora feature. The fungal microbiomes of the three groups displayed distinct beta diversity from each other. Compared with HC group, the abundance of fungal dysbiosis was reflected in a higher ratio of opportunistic fungi in SLE or LN group, as well as the loss of Rhizopus and Malassezia . The main principal components of the flora between the SLE and LN group were generally consistent. The relative abundance of Vanrija in the fecal fungal community was higher in LN group, while the relative abundance of Fusarium was higher in SLE group. Moreover, our data revealed superior diagnostic accuracy for SLE with the fungal species (e.g. Candida , Meyerozyma ). Correlations between gut fungi and clinical parameters were identified by Spearman's correlation analysis. Interestingly, Aspergillus in SLE patients was positively correlated with ACR, 24 h proteinuria, proteinuria, anti-dsDNA, ANA, and SLEDAI, while Rhizopus was negatively correlated with lymphocytes and Hb. Finally, we successfully cultured the fungi and identified it as Candida glabrata by microscopic observation and mass spectrometry., Discussion: We first explored the highly significant gut fungal dysbiosis and ecology in patients with SLE, and demonstrated the applicability of fungal species as SLE diagnostic tools, signifying that the gut fungal mycobiome-host interplay can potentially contribute in disease pathogenesis., Competing Interests: The 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., (Copyright © 2023 Yang, Xu, Chen, Chen, Khan, Li, Zhang, Wang, Xu and Shen.)

With the progression of aquaculture industry, there has been a spurt in dietary supplementation with economically viable medicinal herbs having enough immunostimulatory potential. This also aids in avoidance of environmentally undesirable therapeutics that are almost inevitable to safeguard fish against an array of diseases in aquaculture practices. The study aims to determine the optimal dose of herbs that can stimulate substantial immune response in fish for reclamation of aquaculture. Immunostimulatory potential of the two medicinal herbs- Asparagus racemosus (Shatavari), Withania somnifera (Ashwagandha), individually, and in combination, with a basal diet was screened up to 60 days in Channa punctatus. 300 laboratory acclimatized healthy fish (14 ± 1 g; 11 ± 1 cm) were divided into ten groups- C, S1, S2, S3, A1, A2, A3, AS1, AS2, and AS3, based on the composition of dietary supplementation, in triplicates, with 10 specimens per group. The hematological index, total protein and lysozyme enzyme activity were performed after 30 and 60 days, while qRT-PCR analysis of lysozyme expression was done after 60 days of the feeding trial. The significant (P < 0.05) increments in hematological indices- (TEC, TLC, DLC, Hb, Hct, MCV, MCH and MCHC), total protein content and serum lysozyme activity, after 30 and 60 days; whereas upregulation of lysozyme transcript levels, both in liver and muscle tissues after 60 days of the feeding trial were recorded in groups- AS1, AS2, and AS3. The maximal increment in lysozyme expression was recorded in AS3, both in liver and muscle tissues, with 3.75 ± 0.13 and 3.21 ± 0.18-folds, respectively. However, increments were non-significant (P > 0.05) for MCV in AS2 and AS3 after 30 days; and for MCHC in AS1 for both the durations; whereas in AS2 and AS3, after 60 days of the feeding trial. A positive correlation (P < 0.05) among lysozyme expression, MCH, lymphocytes, neutrophils, total protein content, and serum lysozyme activity in AS3, after 60 days, conclusively, evinces that a 3% dietary supplementation with both A. racemosus and W. somnifera enhances immunity and health profile of the fish, C. punctatus. The study, thus finds ample scope in augmentation of aquaculture production and also paves the way for more researches for biological screenings of potential immunostimulatory medicinal herbs that can be appropriately incorporated in the fish diet., Competing Interests: Declaration of interests None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The co-existence of diabetic ketoacidosis (DKA) with acute pancreatitis (AP) is associated with unfavorable clinical outcomes. However, diagnosing AP in DKA patients is challenging and often missed due to overlapping symptoms. The aim of this retrospective observational study was to compare the clinical characteristics and outcomes of patients with concomitant DKA and AP or DKA alone. Data of patients with DKA admitted between January 2015 to August 2021 to four hospitals in Qatar was extracted from the electronic health record (Cerner). American Diabetes Association criteria and Atlanta criteria were used for DKA and AP diagnosis, respectively. Independent T-test or Mann-Whitney U test was used to analyze continuous variables, whereas categorical variables were analyzed via Chi-square or Fischer exact tests as appropriate. Univariate and multivariate logistic regression models were generated to assess the correlations. A p-value of < 0.05 was considered statistically significant. Of 936 patients with DKA, 84 (9.0%) had coexisting AP. AP was most common in the Asian race (66%, p < 0.001). Patients with DKA and AP were older, had higher admission anion-gap, white cell count, hemoglobin (hb), neutrophil/lymphocyte ratio, urea, creatinine, maximum blood glucose during the episode, total cholesterol and triglyceride level (TGL) (p < 0.05). They had a lower admission venous pH and bicarbonate at 6 h. Patients in the DKA with AP group also had a longer length of stay (LOS), DKA duration and a higher rate of ICU admission (p-values ≤ 0.001). In-hospital mortality, 3-month all-cause readmission, 6-month and 12-month DKA recurrence did not differ between the two groups. Univariate logistic regression analysis showed age, Asian ethnicity, male gender, T2D, admission WBC count, hb, urea, creatinine, potassium, venous pH, bicarbonate, anion gap, total cholesterol, TGL and LDL level were significantly associated with the development of DKA with AP (p < 0.05). In multivariate logistic regression analysis, age and total cholesterol level were associated with concomitant DKA and AP (p < 0.05). Patients with concomitant DKA and AP have more severe derangement in markers of DKA severity, inflammation, kidney injury and metabolic profile, along with a longer DKA duration, LOS and requirement for ICU support compared to DKA patients without AP. This highlights the clinical significance of diagnosing the co-existence of DKA with AP, as the combination results in significantly worse clinical outcomes and greater healthcare utilization than in patients with only DKA., (© 2023. The Author(s).)