bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Race on Progression-Free Survival and Overall Survival in Patients with Multiple Myeloma
Authors: Wani Kashmira , Gutta Radhika , Mittal Aayush , Jamil Maria , Springer Kylie , Kuriakose Philip 
Published: December 2023

Background: Multiple myeloma (MM) is a disorder of plasma cells. Management typically includes induction therapy, autologous stem-cell transplantation (ASCT) and maintenance therapy. Despite significant progress in treatment modalities and improved survival and response rates in patients diagnosed with MM, it remains an incurable disease with a poor outcome, especially in high-risk groups. Black patients have been shown to have a higher incidence of MM than white patients. Multiple studies have been done to examine racial disparities among white and black patients, specifically in overall survival (OS) and progression free survival (PFS). However, data has been overall inconclusive with some studies suggesting there is a difference in survival based on race, while other studies suggesting the opposite. Thus, racial disparities among white and black patients' needs to be further investigated. In our retrospective chart review we reviewed all adult patients with advanced MM within Henry Ford Cancer Institute in the last 10 years to determine the impact of maintenance therapy on PFS and overall survival OS.
Methods: We conducted a retrospective chart review of adult patients with MM who underwent autologous stem cell transplantation (ASCT) between January 1, 2012 to December 31, 2022. Those who received maintenance chemotherapy after transplant were included in the study. Patients who were lost to follow-up or who had largely incomplete records were excluded. Data points including age, gender, race, date of transplant, maintenance chemotherapy regimen, last follow-up, and date of death (if applicable) were recorded. Kaplan-Meier plots were used to illustrate overall survival and time to relapse between various races. Statistical significance was set at p&lt;0.05.
Results: There were 158 patients included in the study. Of the 158 patients, 82 (51.9%) were male, and 76 (48.1%) were female. The average age of patients included was 61.66 + 9.30 years, spanning from 32 to 78 years old. There were 71 (44.9%) White patients, 76 (48.1%) Black patients, and 11 (7.0%) patients that were of another race. There was no statistical significance in PFS and OS between Black, White and Other race categories.
Conclusions: We did not see a difference in outcome based on race and believe all patients would derive equal benefit from maintenance therapy. Further prospective studies are warranted to examine racial disparities in patients with multiple myeloma.
Association between Heavy Metal Exposure and Idiopathic Aplastic Anemia in Adolescents and Adults:a Case Control Study from Northern India
Authors: Jain Arihant , Wadhera Sarthak , Malhotra Pankaj , Singh Charanpreet , Lad Deepesh Pravinkumar , Khadwal Alka Rani , Prakash Gaurav , Varma Neelam , Reddy Prabhakar 
Published: December 2023

Introduction:Compared to western world the incidence of AA in South Asian countries is higher. There are studies to suggest that incidence of this disease is 2-3 times higher in LMICs. Besides immune mediated pathophysiology and inherited presdispostion, toxic insult to the hematopoietic elements due to chemotherapy, radiation exposure, drugs,and environmental toxins such as pesticides and heavy metals have been associated with Aplastic Anemia.The higher incidence of AA in lower socio-economic status and its association with drinking water habits, industrial exposure suggests a possible link with heavy metals in the pathogenesis of disease.
Methodology:Fifty patients diagnosed with idiopathic aplastic anaemia and 50 age and gender matched healthy controls were included in the study. 2 ml of blood and 20 hair shafts were collected as samples from each subject for the analysis of arsenic, lead, cadmium, mercury, and thallium in both samples by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Results:The total study population consisted of 61 males and 39 females. 42% of the cases were residents of rural areas, and 58% belonged to urban areas. 54% participants among the controls belonged to rural areas. Among the total population, 48% cases and 58% controls were using tap water as major source of water. Out of the total participant in the study, 10% of the cases and 12% of the controls were found to be exposed to pesticides previously, however no direct occupational exposure of heavy metal was found among the study population. Twenty-three patients (46%) had NSAA, and 15 patients had SAA (30%) while 12 patients (24%) had VSAA.Mean values of arsenic in blood of patients and controls are 3.52±2.9mcg/L,and 0.0mcg/L respectively and the difference was statistically significant (p &lt;0.001) however the mean arsenic values in hair of cases and controls were not different significantly(0.13±0.1mg/g and 0.15±0.1mg/g;p=0.16).Mean values of cadmium in blood of patients and controls were 2.5±1.9mcg/L and 0 mcg/L (p &lt;0.001). Mean values of cadmium in hair of patients and controls are 0.10±0.16, 0.13±0.28 respectively.We noticed blood cadmium higher than safer limits in 24% of cases none in the controls.We found 6% of cases had higher than permissible limit of mercury level and 8% of cases have higher than permissible limit of lead level in their hair samples which represent chronic exposure.
Conclusion:
We found higher mean values of blood Arsenic and blood Cadmium in cases compared to controls. Upto one fourth cases had higher than safety levels of cadmium in their blood. Although causal association cannot be determined in this study our results indicate that heavy metal toxicity may be one of the reasons for AA in regions with higher environmental exposure and soil and water contamination.
Tmprss6 siRNA Treatment in Mice Stops Hepcidin Reduction across Pregnancy
Authors: Fielding Katherine , Ataide Ricardo , Bennett Cavan , Pettikiriarachchi Anne , Clucas Danielle , Schaeper Ute , Pasricha Sant-Rayn 
Published: December 2023

Aim: Hepcidin levels are suppressed during human and murine pregnancy. It is unknown whether hepcidin levels are primarily the result of iron deficiency/utilisation or whether there is a pregnancy-specific mechanism for hepcidin suppression. We reasoned that Tmprss6 inhibition would cause constitutive BMP-SMAD signalling and help determine the mechanism of antenatal hepcidin suppression.
Method: Female wildtype C57BL/6 mice were treated subcutaneously every 21 days with a GalNAc-siRNA conjugate targeting Tmprss6 (Silence Therapeutics GmbH, Berlin, Germany) or a non-targeting control (NTC) siRNA conjugate. Mice were mated and monitored for pregnancy. Samples were collected from pregnant mice humanely euthanised at E8.5 or E14.5, and unmated controls.
Results: Treatment with Tmprss6 siRNA inhibited hepatic Tmprss6 mRNA expression (unmated fold change 0.077, p&lt;0.0001).
qPCR Hamp expression was significantly increased in Tmprss6 siRNA-treated mice, compared to NTC-treated mice, at all timepoints. Serum hepcidin, by ELISA, was higher in Tmprss6 siRNA-treated mice than in NTC-treated mice at E14.5 (1126ng/ml vs 178.5, p&lt;0.0001). In unmated mice, serum hepcidin was not significantly elevated (640.9 vs 980.1ng/ml, p=0.224).
Across NTC treated pregnancy, Hamp expression and serum hepcidin were reduced at E14.5 compared to unmated ( Hamp fold change E14.5 0.293, p=0.0367; serum hepcidin E14.5 178.5 vs 640.9, p=0.0247). In contrast, Tmprss6 siRNA treatment caused elevated hepcidin through pregnancy (E14.5 1126 vs unmated 980ng/ml, p=0.99); Fig 1a.
Maternal liver iron was unchanged between groups. Tmprss6 siRNA reduced placental iron, fetal liver iron, and fetal weight (0.189 vs 0.226g, p&lt;0.0001), Fig 1b. At E8.5/E14.5, Tmprss6 siRNA reduced Mean Cell Volume (E14.5: 41.42 vs 51.72fL, p&lt;0.0001) and Mean Cell Haemoglobin (E14.5: 11.20 vs 15.68pg, p&lt;0.0001); at E14.5 only, maternal anaemia was seen with Tmprss6 siRNA (haemoglobin 9.4 vs 13.85g/L, p=0.0004).
Conclusion: Disruption of Tmprss6 increased hepcidin and ablated the hepcidin fall over pregnancy. This may suggest that any pregnancy-related factor which directly suppresses hepcidin cannot overcome Tmprss6 knockdown. Tmprss6 siRNA treatment resulted in iron-restricted erythropoiesis, reduced placental iron and impacted fetal development, despite unchanged liver iron stores.
Socioeconomic determinants of the biology and outcomes of acute lymphoblastic leukemia in adults
Authors: Johnston Hannah , Youshanlouei Hamed Rahmani , Osei Clinton , Patel Anand A. , DuVall Adam , Wang Peng , Wanjari Pankhuri , Segal Jeremy , Venkataraman Girish , Cheng Jason X. , Gurbuxani Sandeep , Lager Angela , Fitzpatrick Carrie , Thirman Michael , Nawas Mariam , Liu Hongtao , Drazer Michael , Odenike Olatoyosi , Larson Richard , Stock Wendy , Saygin Caner 
Published: December 2023

Abstract
Various socioeconomic and biologic factors affect cancer health disparities and differences in health outcomes. To better characterize the socioeconomic vs biologic determinants of acute lymphoblastic leukemia (ALL) outcomes, we conducted a single-institution, retrospective analysis of adult patients with ALL treated at the University of Chicago (UChicago) from 2010 to 2022 and compared our outcomes with the US national data (the Surveillance, Epidemiology, and End Results [SEER] database). Among 221 adult patients with ALL treated at UChicago, BCR::ABL1 was more frequent in patients with higher body mass index (BMI; odds ratio [OR], 7.64; 95% confidence interval [CI], 1.17-49.9) and non-Hispanic Black (NHB) ancestry (59% vs 24% in non-Hispanic White (NHW) and 20% in Hispanic patients; P = .001). In a multivariable analysis, age (hazard ratio [HR], 6.93; 95% CI, 2.27-21.1) and higher BMI at diagnosis (HR, 10.3; 95% CI, 2.56-41.5) were independent predictors of poor overall survival (OS). In contrast, race or income were not predictors of OS in the UChicago cohort. Analysis of the national SEER database (2010-2020) demonstrated worse survival outcomes in Hispanic and NHB patients than in NHW patients among adolescent and young adults (AYAs) but not in older adults (aged &gt;40 years). Both AYA and older adult patients with higher median household income had better OS than those with lower income. Therefore, multidisciplinary medical care coupled with essential supportive care services offered at centers experienced in ALL care may alleviate the socioeconomic disparities in ALL outcomes in the United States.
Salmonella enterica in farm environments in the Ashanti Region of Ghana
Authors: Ofori Linda Aurelia , Fosu Dennis , Ofori Seth , Akenten Charity Wiafe , Flieger Antje , Simon Sandra , Jaeger Anna , Lamshöft Maike , May Juergen , Obiri-Danso Kwasi , Phillips Richard , Chercos Daniel Haile , Paintsil Ellis Kobina , Dekker Denise 
Published: November 2023

Abstract
Background
Salmonella enterica are important foodborne pathogens and the third leading cause of death among diarrheal infections worldwide. This cross-sectional study investigated the frequency of antibiotic-resistant Salmonella enterica in commercial and smallholder farm environments in the Ashanti Region of Ghana. A total of 1490 environmental samples, comprising 800 (53.7%) soil (from poultry, pigs, sheep, goats and cattle farms), 409 (27.4%) pooled poultry fecal and 281 (18.9%) dust (from poultry farms) samples, were collected from 30 commercial and 64 smallholder farms. All samples were processed using standard culture methods. Isolates were identified by biochemical methods and confirmed using the VITEK 2 System. Antibiotic susceptibility testing was carried out by disk diffusion following the EUCAST guidelines. Serotyping was performed using the Kauffman White Le Minor Scheme.

Results
The overall Salmonella frequency was 6.0% (n/N = 90/1490); the frequency varied according to the type of sample collected and included: 8.9% for dust (n/N = 25/281), 6.5% for soil (n/N = 52/800) and 3.2% for pooled poultry fecal samples (n/N = 13/409). Salmonella was also recovered from commercial farm environments (8.6%, n/N = 68/793) than from smallholder farms (3.2%, n/N = 22/697) (PR = 2.7, CI: 1.7 – 4.4). Thirty-four different Salmonella serovars were identified, the two most common being Rubislaw (27.8%, n/N = 25/90) and Tamale (12.2%, n/N = 11/90). Serovar diversity was highest in strains from soil samples (70.6%, n/N = 24/34) compared to those found in the dust (35.2%, n/N = 12/34) and in fecal samples (29.4%, n/N = 10/34). Salmonella frequency was much higher in the rainy season (8.4%, n/N = 85/1007) than in the dry season (1.0%, n/N = 5/483) (PR = 8.4, 95% CI: 3.3 – 20.0). Approximately 14.4% (n/N = 13/90) of the isolates were resistant to at least one of the tested antimicrobials, with 84.6% (n/N = 11/13) being resistant to multiple antibiotics. All Salmonella Kentucky (n = 5) were resistant to ciprofloxacin.

Conclusion
This study showed that farm environments represent an important reservoir for antibiotic-resistant Salmonella, which warrants monitoring and good husbandry practices, especially in commercial farms during the rainy season, to control the spread of this pathogen.
The effect of regional transmural agreements on the information transfer of frail older patients
Authors: Fritsche G. , Schoonenboom N. , Van der Kroon H. , Douma CE. , Van der Dussen J. , Verlaan MNE. , Cloosterman B. , Heems M. , Nepal A. , Toor E. J. , de Rooij A. , van Stralen KJ. , Lucke JA. 
Published: November 2023

Abstract
Introduction
Frail older patients are at risk for many complications when admitted to the hospital. Multidisciplinary regional transmural agreements (RTA) in which guidelines were set concerning the information transfer of frail older patients might improve outcomes. We aim to investigate the effect of implementation of the RTA on the completeness of the information transfer of frail older patients when admitted to and discharged from the hospital.

Methods
This is a retrospective cohort study in which we collected data from 400 randomly selected hospitalized frail older patients (70+) before the implementation of the RTA, January through March 2021, and after, October through December 2021. The cohort was split up into four groups, which determined what correspondence would be checked (referral letter by General Practitioner (GP) and three groups of ‘hospital letters’: ED letter upon admittance, clinical discharge letter to the elderly care physician and clinical discharge letter to the GP. We assessed for mention of frailty, a medication list and mention of resuscitation orders.

Results
In the period before implementation the mean age of patients was 82.6 years (SD 7.4) and 101 were female (50.5%), after implementation mean age was 82.3 (SD 6.9) and 112 were female (56.0%). Frailty was mentioned in hospital letters in 12.7% before and 15.3% after implementation (p = 0.09). More GP referral letters were present after implementation (32.0% vs. 54.0%, p = 0.03), however frailty was mentioned only in 12.5% before and 7.4% after (p = 0.58). There was a good handover of medication lists from the hospital (89.3% before, 94% after, p = 0.20) and even better from the GP (93.8% before, 100% after, p = 0.19). Resuscitation orders were mentioned in 59.3% of letters from the hospital before implementation and 57.3% after (p = 0.77), which is higher than in the referral letters (18.8% before and 22.2% after (p = 0.91).

Discussion
The implementation of RTA improved the number of GP referral letters present; however, it did not lead to other significant improvements in communication between the hospital and the GP’s. Frailty and resuscitation orders are still frequently not mentioned in the reports. After a successful reimplementation, the improvements of outcomes could be investigated.
Association between disability in activities of daily living and phase angle in hemodialysis patients
Authors: Li Junhui , Wang Zhi , Zhang Qiannan , Zhang Huiping , Shen Yuxin , Zhang Qi , Jian Guihua , Cheng Dongsheng , Wang Niansong 
Published: November 2023

Abstract
Background
Disability in activities of daily living (ADL) significantly increases the risk of mortality among patients undergoing hemodialysis. Malnutrition and decreased exercise capacity are closely correlated with ADL disability. Phase angle (PhA) has been proposed as a measure of nutritional status and exercise capacity. This study aims to investigate the prevalence of ADL disability in hemodialysis patients and its association with PhA.

Methods
A prospective, observational study was conducted, involving hemodialysis patients treated between November 2019 and January 2020 in an affiliated hospital of Chinese university. ADL was measured using both basic ADL (BADL) scales and instrumental ADL (IADL) scales. PhA measurements were obtained using a BIA device while the patients were in the supine position after dialysis.

Results
A total of 237 hemodialysis patients with a mean age of 60.01 ± 13.55 years were included in this study. The prevalence of disability in ADL was 43.5%. Multivariable analysis results showed a robust association between low PhA and disability in both BADL and IADL (for each unit decrease in PhA: odds ratio 4.83 [95% CI: 2.56–9.0], and 3.57 [95% CI: 2.14–5.95], respectively). The optimal cut-off values of PhA for disability in BADL and IADL were 4.8 and 5.4, with the area under the ROC curve (AUC) were 0.783 (0.727, 0.835) and 0.799 (0.743, 0.848), respectively.

Conclusions
Low PhA is strongly associated with disability in ADL in hemodialysis patients. These findings suggest that PhA may serve as a potentially objective measure of ADL disability in hemodialysis patients.
Genetic detection of two novel LRP5 pathogenic variants in patients with familial exudative vitreoretinopathy
Authors: Li Jiayu , Wang Chanjuan , Zhang Shaochi , Cai Bo , Pan Bo , Sun Caihong , Qi Xiaolong , Ma Chunmei , Fang Wei , Jin Kangxin , Bi Xiaojun , Jin Zibing , Zhuang Wenjuan 
Published: November 2023

Abstract
Background
Familial exudative vitreoretinopathy (FEVR) is a genetic eye disorder that leads to abnormal development of retinal blood vessels, resulting in vision impairment. This study aims to identify pathogenic variants by targeted exome sequencing in 9 independent pedigrees with FEVR and characterize the novel pathogenic variants by molecular dynamics simulation.

Methods
Clinical data were collected from 9 families with FEVR. The causative genes were screened by targeted next-generation sequencing (TGS) and verified by Sanger sequencing. In silico analyses (SIFT, Polyphen2, Revel, MutationTaster, and GERP + +) were carried out to evaluate the pathogenicity of the variants. Molecular dynamics was simulated to predict protein conformation and flexibility transformation alterations on pathogenesis. Furthermore, molecular docking techniques were employed to explore the interactions and binding properties between LRP5 and DKK1 proteins relevant to the disease.

Results
A 44% overall detection rate was achieved with four variants including c.4289delC: p.Pro1431Argfs*8, c.2073G > T: p.Trp691Cys, c.1801G > A: p.Gly601Arg in LRP5 and c.633 T > A: p.Tyr211* in TSPAN12 in 4 unrelated probands. Based on in silico analysis and ACMG standard, two of them, c.4289delC: p.Pro1431Argfs*8 and c.2073G > T: p.Trp691Cys of LRP5 were identified as novel pathogenic variants. Based on computational predictions using molecular dynamics simulations and molecular docking, there are indications that these two variants might lead to alterations in the secondary structure and spatial conformation of the protein, potentially impacting its rigidity and flexibility. Furthermore, these pathogenic variants are speculated to potentially influence hydrogen bonding interactions and could result in an increased binding affinity with the DKK1 protein.

Conclusions
Two novel genetic variants of the LRP5 gene were identified, expanding the range of mutations associated with FEVR. Through molecular dynamics simulations and molecular docking, the potential impact of these variants on protein structure and their interactions with the DKK1 protein has been explored. These findings provide further support for the involvement of these variants in the pathogenesis of the disease.
Endoscopic spinal cord untethering using a 1 cm skin incision technique in pediatrics: a technical case report
Authors: Ishisaka Eitaro , Tahara Shigeyuki , Tsukiyama Atsushi , Nozaki Toshiki , Hattori Yujiro , Morita Akio , Murai Yasuo 
Published: November 2023

Abstract
Background
Spinal cord untethering by sectioning the filum terminale is commonly performed in tethered cord syndrome patients with minor abnormalities such as filar lipoma, thickened filum terminale, and low conus medullaris. Our endoscopic surgical technique, using the interlaminar approach, allows for sectioning the filum terminale through a very small skin incision. To our knowledge, this procedure has not been previously reported. This is the first case report involving a 1 cm skin incision.

Case presentation
A 9-month-old male patient was referred to our neurosurgical department due to a coccygeal dimple. MRI revealed a thickened fatty filum. After considering the treatment options for this patient, the parents agreed to spinal cord untethering. A midline 1 cm skin incision was made at the L4/5 vertebral level. Untethering by sectioning the filum terminale was performed by full endoscopic surgery using the interlaminar approach. The procedure was uneventful and there were no postoperative complications.

Conclusions
In terms of visibility and minimizing invasiveness, our surgical technique of using the interlaminar approach with endoscopy allows for untethering by sectioning the filum terminale through a very small skin incision.
Impairment of delayed recall as a predictor of amnestic mild cognitive impairment development in normal older adults: a 7-year of longitudinal cohort study in Shanghai
Authors: Bao Xiaoqian , Li Wei , Liu Yuanyuan , Li Xia , Yue Ling , Xiao Shifu 
Published: November 2023

Abstract
Background
Amnestic mild cognitive impairment (aMCI) is considered a prodromal phase of Alzheimer’s disease (AD). However, little is known about the neuropsychological characteristic at pre-MCI stage. This study aimed to investigate which neuropsychological tests could significantly predict aMCI from a seven-year longitudinal cohort study.

Methods
The present study included 123 individuals with baseline cognitive normal (NC) diagnosis and a 7-year follow-up visit. All the subjects were from the China Longitudinal Aging Study (CLAS) study. Participants were divided into two groups, non-converter and converter based on whether progression to aMCI at follow-up. All participants underwent standardized comprehensive neuropsychological tests, including the mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), auditory verbal learning test (AVLT), the digital span test, the verbal fluency test, the visual recognition test, the WAIS picture completion task, and WAIS block design. Logistic regression analysis was used to evaluate the predictive power of baseline cognitive performance for the transformation of amnestic mild cognitive impairment. Receiver operating characteristic (ROC) curve was used to test the most sensitive test for distinguishing different groups.

Results
Between the non-converter group and converter group, there were significant differences in the baseline scores of AVLT-delayed recall (AVLT-DR) (8.70 ± 3.61 vs. 6.81 ± 2.96, p = 0.001) and WAIS block design (29.86 ± 7.07 vs. 26.53 ± 8.29, p = 0.041). After controlling for gender, age, and education level, converter group showed lower baseline AVLT-DR than non-converter group, while no significant difference was found in WAIS block design. Furthermore, converter group had lower AVLT-DR score after controlling for somatic disease. The area under the curve of regression equation model was 0.738 (95%CI:0.635–0.840), with a sensitivity 83.9%, specificity of 63.6%.

Conclusions
Our results proved the value of delayed recall of AVLT in predicting conversion to aMCI. Early and careful checking of the cognitive function among older people should be emphasized.