bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment
Authors: Miladinia Mojtaba , Jahangiri Mina , White Sharon Jackson , Karimpourian Hossein , Inno Alessandro , Chan Sally Wai-Chi , Ganji Reza , Maniati Mahmood , Zarea Kourosh , Ghalamkari Marziyeh , Farahat Ali , Fagerström Cecilia 
Published: April 2024

AbstractBackgroundCancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer.MethodsThe 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups.DiscussionThe findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines.Trial registrationIRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.
NODAL variants are associated with a continuum of laterality defects from simple D-transposition of the great arteries to heterotaxy
Authors: Dardas Zain , Fatih Jawid M. , Jolly Angad , Dawood Moez , Du Haowei , Grochowski Christopher M. , Jones Edward G. , Jhangiani Shalini N. , Wehrens Xander H. T. , Liu Pengfei , Bi Weimin , Boerwinkle Eric , Posey Jennifer E. , Muzny Donna M. , Gibbs Richard A. , Lupski James R. , Coban-Akdemir Zeynep , Morris Shaine A. 
Published: April 2024

Abstract
Background
NODAL signaling plays a critical role in embryonic patterning and heart development in vertebrates. Genetic variants resulting in perturbations of the TGF-β/NODAL signaling pathway have reproducibly been shown to cause laterality defects in humans. To further explore this association and improve genetic diagnosis, the study aims to identify and characterize a broader range of NODAL variants in a large number of individuals with laterality defects.

Methods
We re-analyzed a cohort of 321 proband-only exomes of individuals with clinically diagnosed laterality congenital heart disease (CHD) using family-based, rare variant genomic analyses. To this cohort we added 12 affected subjects with known NODAL variants and CHD from institutional research and clinical cohorts to investigate an allelic series. For those with candidate contributory variants, variant allele confirmation and segregation analysis were studied by Sanger sequencing in available family members. Array comparative genomic hybridization and droplet digital PCR were utilized for copy number variants (CNV) validation and characterization. We performed Human Phenotype Ontology (HPO)-based quantitative phenotypic analyses to dissect allele-specific phenotypic differences.

Results
Missense, nonsense, splice site, indels, and/or structural variants of NODAL were identified as potential causes of heterotaxy and other laterality defects in 33 CHD cases. We describe a recurrent complex indel variant for which the nucleic acid secondary structure predictions implicate secondary structure mutagenesis as a possible mechanism for formation. We identified two CNV deletion alleles spanning NODAL in two unrelated CHD cases. Furthermore, 17 CHD individuals were found (16/17 with known Hispanic ancestry) to have the c.778G > A:p.G260R NODAL missense variant which we propose reclassification from variant of uncertain significance (VUS) to likely pathogenic. Quantitative HPO-based analyses of the observed clinical phenotype for all cases with p.G260R variation, including heterozygous, homozygous, and compound heterozygous cases, reveal clustering of individuals with biallelic variation. This finding provides evidence for a genotypic-phenotypic correlation and an allele-specific gene dosage model.

Conclusion
Our data further support a role for rare deleterious variants in NODAL as a cause for sporadic human laterality defects, expand the repertoire of observed anatomical complexity of potential cardiovascular anomalies, and implicate an allele specific gene dosage model.
Unicentric Castleman’s disease in the parotid gland associated with psoriasis: a case report
Authors: Zhang Ying , Li Chong-Yang , Li Zhi , Chen Wei 
Published: April 2024

Abstract
Background
Castleman’s disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman’s disease due to its unclear pathogenesis.

Case presentation
We present a Castleman’s disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman’s disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman’s disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased.

Conclusions
Clinicians should be aware of the possibility of Castleman’s disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6.
Receipt of prescription opioid medication is associated with increased mortality in an Israeli population
Authors: Cohen Matan J. , Dressler Reuven L. , Kaliner Ehud 
Published: April 2024

Abstract
Background
Despite Israel’s increased use of prescription opioids, reported deaths resulting or associated with opioids have decreased, in fact dramatically, since 2005. This contrast is unique and difficult to explain. We sought to examine whether higher prescribed opioid dosages among adults without oncologic diagnoses were associated with higher all-cause mortality rates.

Methods
A historical cohort study in Clalit Health Services, using a data repository including all adult patients prescribed opiates between 2010 and 2020, excluding patients with oncologic diagnoses. Patients were classified into three groups according to opioid use: below 50 Morphine milligram equivalents (MME) per day, 50 to 90 MME per day, and above 90 MME per day. Sex, Charlson comorbidity score, age and socioeconomic status were recorded. Mortality rates were compared between the dosage groups and compared to age-standardized mortality rates in the general population.

Results
On multivariate analysis, patients receiving 90 or more MME per day were 2.37 (95%CI 2.1 to 2.68) more likely to have died compared to patients receiving below 50 MME per day. The respective hazard ratio among patients receiving between 50 and 90 MME per day was 2.23 (2.01 to 2.46). Among patients aged 18 to 50, standardized mortality ratios (SMRs) compared to the general population ranged between 5.4 to 8.6 among women, receiving between 50 and 90 MME per day, and between 8.07 and 10.7 among women receiving 90 or more MME per day. The respective SMRs among men were 1.2 to 3.8 and 2.7 to 5.4.

Conclusion
Increased opioid use is independently associated with increased all-cause mortality among non-oncological patients. This result is most notable among young adults with little or no known comorbidities. These findings are consistent with results in other countries and seem more credible than previous Israeli reports. Healthcare regulators and providers should, therefore, act to curtail the increasing opioid prescriptions and devise and enhance controls in the healthcare system, which, until 2020, had very limited mechanisms in place.
Object tracking method based on edge detection and morphology
Authors: Xu Jie , Niu Sijie , Wang Zhifeng 
Published: April 2024

AbstractWith the continuous development of science and technology, intelligent surveillance technology using image processing and computer vision is also progressing. To improve the performance of target detection and tracking, an improved target tracking method is proposed, which uses a combination of the Canny operator and morphology for the detection part, and a Kalman filter extended Kernel Correlation Filter (KCF) tracking algorithm approach for the tracking part. First, a convolution kernel of $$3\times 3$$

3
×
3

is improved to a convolution kernel of $$2\times 2$$

2
×
2

in the traditional Canny algorithm, and the pixel gradient in the diagonal direction is increased. Secondly, a mathematical morphology theory of nonlinear filtering is applied to the Canny edge detection algorithm, and this method effectively improves the clarity of image edges. Finally, the extended kernel correlation filtering algorithm is applied to video surveillance and Online Object Tracking Benckmark2013 (OTB2013) datasets for testing. The experimental results show that the method proposed in this paper can accurately detect moving targets and the algorithm has good accuracy and success rate.
Effects of different types of Ringer’s solution on patients with traumatic haemorrhagic shock: a prospective cohort study
Authors: Li Qing , Yang Qiang , Tian Chao , Guo Yao , Liu Hui , Cheng Yadong , Bi Shu-Zhen , Chen Jin-Hua 
Published: April 2024

Abstract
Objective
To compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock.

Method
We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3−), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation.

Results
The post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer’s solution group had significantly higher pH, cHCO3− and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer’s solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001).

Conclusion
Sodium bicarbonate Ringer’s solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer’s solution in limited fluid resuscitation has positive results and is of high clinical value.
Bone marrow dosimetry in low volume mHSPC patients receiving Lu-177-PSMA therapy using SPECT/CT
Authors: Grob Dagmar , Privé Bastiaan M. , Muselaers Constantijn H. J. , Mehra Niven , Nagarajah James , Konijnenberg Mark W. , Peters Steffie M. B. 
Published: April 2024

Abstract
Background
Bone marrow toxicity in advanced prostate cancer patients who receive [177Lu]Lu-PSMA-617 is a well-known concern. In early stage patients; e.g. low volume metastatic hormone sensitive prostate cancer (mHSPC) patients, prevention of late bone marrow toxicity is even more crucial due to longer life expectancy. To date, bone marrow dosimetry is primarily performed using blood sampling. This method is time consuming and does not account for possible active bone marrow uptake. Therefore other methodologies are investigated. We calculated the bone marrow absorbed dose for [177Lu]Lu-PSMA-617 in mHSPC patients using SPECT/CT imaging and compared it to the blood sampling method as reference.

Methods
Eight mHSPC patients underwent two cycles (3 and 6 GBq) of [177Lu]Lu-PSMA-617 therapy. After each cycle, five time point (1 h, 1 day, 2 days, 3 days, 7 days) SPECT/CT was performed at kidney level. Bone marrow dosimetry was performed using commercial software by drawing ten 1.5 cm diameter spheres in the lowest ten vertebrae to determine the time-integrated activity. Simplified protocols using only 2 imaging time points and 3 vertebrae were also compared. Blood-based dosimetry was based on the blood sampling method according to the EANM guideline.

Results
Mean bone marrow absorbed dose was significantly different (p < 0.01) for the imaging based method (25.4 ± 8.7 mGy/GBq) and the blood based method (17.2 ± 3.4 mGy/GBq), with an increasing absorbed dose ratio between both methods over time. Bland Altman analysis of both simplification steps showed that differences in absorbed dose were all within the 95% limits of agreement.

Conclusion
This study showed that bone marrow absorbed dose after [177Lu]Lu-PSMA-617 can be determined using an imaging-based method of the lower vertebrae, and simplified using 2 time points (1 and 7 days) and 3 vertebrae. An increasing absorbed dose ratio over time between the imaging-based method and blood-based method suggests that there might be specific bone marrow binding of [177Lu]Lu-PSMA-617.
Predictive factors of tinnitus after vestibular schwannoma surgery: a case-control study
Authors: You Na , Zhang Jiashu , Zhang Ding , Zhao Yue , Zhang Jun , Xu Bainan 
Published: April 2024

Abstract
Background
Tinnitus is very common in patients with vestibular schwannoma (VS). We analyzed the related factors of tinnitus after surgery.

Methods
One hundred seventy-three patients diagnosed with unilateral VS operated via the retrosigmoid approach were included in the study. All patients underwent relevant examinations and completed the THI scale before surgery and 6 months after surgery. The prognosis of tinnitus was evaluated according to the changes in THI.

Results
Of the 129 preoperative tinnitus patients, postoperative tinnitus resolved in 12.4%, improved in 29.5%, remained unchanged in 28.6%, and worsened in 29.5%. 18.2% of 44 patients without preoperative tinnitus appeared new-onset tinnitus postoperatively. Thirty-six patients never had tinnitus. Patients with smaller tumor sizes (≤ 3 cm) were more likely to experience preoperative tinnitus. Younger patients and those with serviceable hearing preoperatively were more likely to report their tinnitus unchanged or worsened. A new onset of postoperative tinnitus in the preoperative non-tinnitus group was found in better preoperative hearing function.

Conclusions
In this study, 70% of patients had persistent tinnitus after vestibular schwannoma resection. The prognosis of tinnitus was influenced by age and preoperative hearing function. Tinnitus is a bothersome symptom and is often underestimated by doctors. Assessment of tinnitus is mandatory during the management of vestibular schwannoma.
Modeling time to death for under-five children in Malawi using 2015/16 Demographic and Health Survey: a survival analysis
Authors: Mulagha-Maganga Assa , Kazembe Lawrence , Ndiragu Martin 
Published: April 2024

Abstract
Background
Malawi has one of the highest under-five mortality rates in Sub Sahara Africa. Understanding the factors that contribute to child mortality in Malawi is crucial for the development and implementation of effective interventions to reduce child mortality. The aim of this study is to use survival analysis in modeling time to death for under-five children in Malawi. In turn, identify potential risk factors for child mortality and inform the development of interventions to reduce child mortality in the country.

Method
This study used data from all births that occurred in the five years leading up to the 2015/16 Malawi Demographic and Health Survey. The Frailty hazard model was applied to predict infant survival in Malawi. In this analysis, the outcome of interest was death and it had two possible outcomes: "dead" or "alive". Age at death was regarded as the survival time variable. Infants who were still alive at the time of the study as of the day of the interview were considered as censored observations in the analysis.

Results
A total of 17,286 live births born during the 5 years preceding the survey were analysed. The study found that the risk of death was higher among children born to mothers aged 30–39 and 40 or older compared to teen mothers. Infants whose mothers attended fewer than four antenatal care visits were also found to be at a higher risk of death. On the other hand, the study found that using mosquito nets and early breastfeeding were associated with a lower risk of death, as were being male and coming from a wealthier household.

Conclusion
The study reveals a notable decline in infant mortality rates as under-five children age, underscoring the challenge of ensuring newborn survival. Factors such as maternal age, birth order, socioeconomic status, mosquito net usage, early breastfeeding initiation, geographic location, and child's sex are key predictors of under-five mortality. To address this, public health strategies should prioritize interventions targeting these predictors to reduce under-five mortality rates.
Effects of stigma on the quality of life in patients with epilepsy
Authors: Hu Chunmei , Zhao Yuping , Xiao Zheng 
Published: April 2024

Abstract
Background
This study was aimed to evaluate the stigma and quality of life (QoL) in adult patients with epilepsy (PWEs) and explore the relationship between stigma and QoL.

Methods
Two hundred and ninety-eight PWEs admitted to the Epilepsy Center of the First Affiliated Hospital of Chongqing Medical University during September 2020 and March 2021 were enrolled in this study. All participants completed self-reported questionnaires including the Stigma Scale for Epilepsy and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).

Results
A total of 146 (49%) PWEs reported an experience of stigma. The total score of QOLIE-31 and the individual scores of seven subscales (worry about new seizures, emotion, well-being, energy and fatigue, cognitive impairment, medication effect, and social function) were significantly decreased in these patients (P < 0.001). Multivariate stepwise linear regression analysis showed that the annual household income per capita, the number of antiseizure medications and stigma had statistically significant effects on QoL (P < 0.05). Among them, stigma had the most significant negative effect.

Conclusions
Nearly half of PWEs have experienced stigma. Stigma, lower household income per capita, and polypharmacy treatment are associated with poorer QoL. Stigma has the most obvious negative impact.
Association of single nucleotide polymorphism at BMP2 gene with iron deficiency status among anaemic patients in Hospital Universiti Sains Malaysia
Authors: Azman Nur Ain , Zulkafli Zefarina , Bakar Nur Salwani , Assyuhada Mat Ghani Siti Nor , Mohammad Siti Nur Nabeela A’ifah 
Published: April 2024

Abstract
Background
Iron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status.

Results
104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron.

Conclusions
In future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.
Clinical and epidemiological characterization of eosinophilic ascites in Egypt: a single center experience
Authors: Medhat Mohammed Ahmed , Abdelmalek Mohamed O. , Mekky Mohamed A. , Abd-Elsalam Sherief , Abdel-Malek Mohamed Ahmed Yehya , Ahmed Sayed Hassan , Amry Yusuf S. , Hassan Waleed Attia 
Published: April 2024

Abstract
Background & aims
Eosinophilic ascites is non-common and challenging disease. This study aimed to describe the clinical presentation and treatment of eosinophilic ascites.

Methods
This was a prospective single-center study that included cases with eosinophilic ascites who were admitted to Tropical Medicine and Gastroenterology Department, Assiut University Hospital, Assiut, Egypt, during the period between May 2020 to May 2023. The clinical presentation, investigations, treatment, and follow-up data of the included patients were collected and analyzed.

Results
Seventeen cases of eosinophilic ascites were included in the study. The main presenting manifestations were abdominal pain (47.1%), and abdominal pain with distension (29.4%). Two patients presented with a picture of intestinal obstruction. Moderate ascites was found in 10 patients (58.8%) by ultrasound. Eosinophilia in the peripheral hemogram was detected in 76.5% of the study population. Endoscopic examination showed gastro-duodenitis in 9 patients (52.9%) and duodenitis in 4 patients (23.5%). All patients showed complete improvement and disappearance of ascites after starting steroids within two weeks. Eleven patients (64.7%) relapsed after discontinuation of steroids.

Conclusion
Eosinophilic ascites is an uncommon cause of ascites that is often underdiagnosed. The relapse rate after stopping treatment is high but with excellent response to retreatment.