bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible involvement of sialidase and sialyltransferase activities in a stage-dependent recycling of sialic acid in some organs of type 1 and type 2 diabetic rats
Authors: Erhabor Osas Graham , Obochi Peter , Isah Murtala Bindawa , Usman Mohammed Aliyu , Umar Ismaila Alhaji , Simelane Mthokozisi B. C. , Shuaibu Mohammed Nasir , Islam Md. Shahidul , Ibrahim Mohammed Auwal 
Published: June 2024

BackgroundType 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D.MethodsSialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases.ResultsThe FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum.ConclusionsWe concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus.
Prevalence and risk factors predisposing low bone mineral density in patients with thalassemia
Authors: Ananvutisombat Natnicha , Tantiworawit Adisak , Punnachet Teerachat , Hantrakun Nonthakorn , Piriyakhuntorn Pokpong , Rattanathammethee Thanawat , Hantrakool Sasinee , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Norasetthada Lalita , Fanhchaksai Kanda , Charoenkwan Pimlak 
Published: June 2024

BackgroundA common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients.MethodThis is a cross-sectional study. Eligible patients were males aged within 18–49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model.ResultsPrevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p&lt;0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (β=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (β=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (β=-0.48, 95% CI -0.91 to -0.04, p=0.031).ConclusionThis study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score.
A rare missense p.C125Y mutation in the TNFRSF1A gene identified in a Chinese family with tumor necrosis factor receptor-associated periodic fever syndrome
Authors: Qian Mengqing , Zhou Jingyu , Wu Jing , Zhang Haocheng , Yu Shenglei , Xu Haoxin , Yang Yixuan , Zhou Feiran , Yang Qingluan , Shao Lingyun , Zhang Wenhong , Jiang Ning , Ruan Qiaoling 
Published: June 2024

BackgroundTumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment.MethodsIn this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals.ResultsA typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR.ConclusionThis is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.
Application of whole exome sequencing in carrier screening for high-risk families without probands
Authors: Huang Qinlin , Wang Zhongjie , Teng Yanling , Zhang Wen , Wen Juan , Zhu Huimin , Liang Desheng , Wu Lingqian , Li Zhuo 
Published: June 2024

PurposeThis study aimed to screen the genetic etiology for the high-risk families including those with an adverse pregnancy history, a history of consanguineous marriages, or a history of genetic diseases, but lack of proband via whole exome sequencing (WES).Methods128 individuals from high-risk family were tested by WES. The candidate variants were analyzed according to the ACMG criteria to screen the potential carriers. At-risk couples (ARCs) who harbored the same causative gene were provided with precise fertility guidance to avoid the birth of children with birth defects.ResultsThe total detection rate was 36.72%, with pathogenic/likely pathogenic (P/LP) variants found in 47 individuals, and variants of uncertain significance (VUS) were found in 34. Among couples with adverse pregnancy history: P/LP variants were found in 38 individuals, and VUS were found in 26, for a detection rate of 34.55%; among members of family history of genetic disease or consanguineous marriages: P/LP variants were found in nine individuals, and VUS were found in 8, for a detection rate of 50.00%. Otherwise, we detected 19 ARCs who both carried P/LP variants in the same gene, with a theoretical offspring prevalence of up to 7.42%.ConclusionIn the absence of probands, carrier screening using WES can provide an efficient tool for screening the molecular etiology of high-risk families.
Early versus delayed enteral nutrition in ICU patients with sepsis: a propensity score-matched analysis based on the MIMIC-IV database
Authors: Xu Fuchao , Xu Jianxin , Ma Jinjin , Xu Wenbo , Gu Shuangshuang , Lu Geng , Wang Jun 
Published: June 2024

BackgroundEarly enteral nutrition (EN) is recommended for sepsis management, but its optimal timing and clinical benefits remain uncertain. This study evaluates whether early EN improves outcomes compared to delayed EN in patients with sepsis.MethodsWe analyzed data of septic patients from the MIMIC-IV 2.2 database, focusing on those in the Medical Intensive Care Unit (MICU) and Surgical Intensive Care Unit (SICU). Patients who initiated EN within 3 days were classified into the early EN group, while those who started EN between 3 and 7 days were classified into the delayed EN group. Propensity score matching was used to compare outcomes between the groups.ResultsAmong 1,111 patients, 786 (70.7%) were in the early EN group and 325 (29.3%) were in the delayed EN group. Before propensity score matching, the early EN group demonstrated lower mortality (crude OR = 0.694; 95% CI: 0.514–0.936; p = 0.018) and shorter ICU stays (8.3 [5.2, 12.3] vs. 10.0 [7.5, 14.2] days; p &lt; 0.001). After matching, no significant difference in mortality was observed. However, the early EN group had shorter ICU stays (8.3 [5.2, 12.4] vs. 10.1 [7.5, 14.2] days; p &lt; 0.001) and a lower incidence of AKI stage 3 (49.3% vs. 55.5%; p = 0.030). Subgroup analysis revealed that early EN significantly reduced the 28-day mortality rate in sepsis patients with lactate levels ≤4 mmol/L, with an adjusted odds ratio (aOR) of 0.579 (95% CI: 0.361, 0.930; p = 0.024).ConclusionEarly enteral nutrition may not significantly reduce overall mortality in sepsis patients but may shorten ICU stays and decrease the incidence of AKI stage 3. Further research is needed to identify specific patient characteristics that benefit most from early EN.
Development and validation of a nomogram to predict poor efficacy of imatinib in the treatment of newly diagnosed chronic phase chronic myeloid leukemia patients
Authors: Li Yuxin , Zhang Yilin , Wang Jin , He Aili , Zhang Wanggang , Cao Xingmei , Chen Yinxia , Liu Jie , Zhang Pengyu , Wang Jianli , Zhao Wanhong , Yang Yun , Meng Xin , Chen Sheping , Zhang Longjin , Wang Ting , Wang Xugeng , Ma Xiaorong 
Published: June 2024

BackgroundImatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system.MethodsWe retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi’an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores.ResultsThe area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778–0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P &lt; 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P&lt;0.05).ConclusionWe constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.
Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats
Authors: Getsy Paulina M. , May Walter J. , Young Alex P. , Baby Santhosh M. , Coffee Gregory A. , Bates James N. , Hsieh Yee-Hsee , Lewis Stephen J. 
Published: June 2024

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200 μmol/kg, IV), worsens the adverse actions of fentanyl (75 μg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.
Optimising desired gain indices to maximise selection response
Authors: Joukhadar Reem , Li Yongjun , Thistlethwaite Rebecca , Forrest Kerrie L. , Tibbits Josquin F. , Trethowan Richard , Hayden Matthew J. 
Published: June 2024

IntroductionIn plant breeding, we often aim to improve multiple traits at once. However, without knowing the economic value of each trait, it is hard to decide which traits to focus on. This is where “desired gain selection indices” come in handy, which can yield optimal gains in each trait based on the breeder’s prioritisation of desired improvements when economic weights are not available. However, they lack the ability to maximise the selection response and determine the correlation between the index and net genetic merit.MethodsHere, we report the development of an iterative desired gain selection index method that optimises the sampling of the desired gain values to achieve a targeted or a user-specified selection response for multiple traits. This targeted selection response can be constrained or unconstrained for either a subset or all the studied traits.ResultsWe tested the method using genomic estimated breeding values (GEBVs) for seven traits in a bread wheat (Triticum aestivum) reference breeding population comprising 3,331 lines and achieved prediction accuracies ranging between 0.29 and 0.47 across the seven traits. The indices were validated using 3,005 double haploid lines that were derived from crosses between parents selected from the reference population. We tested three user-specified response scenarios: a constrained equal weight (INDEX1), a constrained yield dominant weight (INDEX2), and an unconstrained weight (INDEX3). Our method achieved an equivalent response to the user-specified selection response when constraining a set of traits, and this response was much better than the response of the traditional desired gain selection indices method without iteration. Interestingly, when using unconstrained weight, our iterative method maximised the selection response and shifted the average GEBVs of the selection candidates towards the desired direction.DiscussionOur results show that the method is an optimal choice not only when economic weights are unavailable, but also when constraining the selection response is an unfavourable option.
Feasibility, acceptability, and appropriability of a national whole-school program for reducing school violence and improving school coexistence
Authors: Rojas-Andrade Rodrigo , Lopez Leiva Verónica , Varela Jorge J. , Soto García Pamela , Álvarez Juan Pablo , Ramirez María Teresa 
Published: June 2024

IntroductionThe increase in school violence following the COVID-19 pandemic underscores the need for schools to adopt a multilevel whole-school approach. This study examines a national program designed by the Chilean Ministry of Education, in collaboration with universities, as part of the Ministry’s Educational Reactivation Plan, aimed at improving school climate management across Chile.MethodsThe “Learning to Live Together Program” (LLT) was implemented across all 16 regions of Chile, focusing on establishing school climate networks, providing direct intensive university technical assistance, and enhancing professional development and training. The feasibility, acceptability, and appropriability of the LLT program were assessed through a survey distributed to 1,561 staff members from 783 schools. Participants responded to a comprehensive set of instruments measuring acceptability, appropriability, feasibility, attitudes toward implementation, fidelity, and initial perceived results.ResultsThe results indicate high initial adoption rates and significant improvements in the assessed dimensions. The enhancement of school climate practices and strengthening school collaboration networks were of considerable relevance.DiscussionThese findings support the efficacy of the multilevel whole-school approach as a viable strategy for Latin American countries, providing critical data for educational and governmental decision-making. Furthermore, this study provides evidence that these outcomes may be applicable to the implementation of similar policies in different contexts and countries.
Ketamine in the effective management of chronic pain, depression, and posttraumatic stress disorder for Veterans: A meta-analysis and systematic review
Authors: Liu Jenny J.W. , Ein Natalie , Gervasio Julia , Baker Clara , Plouffe Rachel , Wanklyn Sonya , Burhan Amer M. , Lau Brenda , Abreu Emmanuel , Wasiuta Thomas , Nazarov Anthony , Richardson J. Don 
Published: June 2024

IntroductionKetamine has emerged as a promising treatment alternative for the management of chronic pain. Despite encouraging findings in civilian populations, and favourable results from trials examining its efficacy in military populations, there is still a dearth of information pointing to optimal specifications related to ketamine administration for pain, depression, and posttraumatic stress disorder (PTSD) in military populations. This meta-analysis and systematic review synthesised available evidence on the effectiveness, tolerability, and feasibility of ketamine in the management of chronic pain and mental health conditions in military populations.MethodsThis review followed the Cochrane’s Guide for systematic reviews of interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as frameworks for data collection and synthesis.ResultsA total of 11 studies and 22 independent samples were retained for data analyses. Across samples, improvements in pain, depression, and PTSD outcomes were evident, with the use of ketamine leading to significant reductions, g = 1.76, SE = 0.19, 95% CI (1.39, 2.13), Z = 9.26, p &lt;.001. These effect sizes were robust with moderate-to-large effects. In addition, the reductions in symptoms were observed in both active-duty and Veteran groups, and for different routes of ketamine administration, frequencies of ketamine administration, duration of ketamine treatments, dosage, study design, and allowance for concurrent treatments.DiscussionThis review provides a preliminary synthesis of available evidence which suggests that ketamine may be a potential option for the treatment of depression, PTSD, and chronic pain in military populations. The viability of ketamine as an alternative treatment may be particularly impactful for those who are treatment resistant, experience chronic symptoms, and/or have exhausted conventional treatments. More research is warranted in order verify the findings presented in this review.
Prevalence of burnout and associated factors among midwives, 2023: institution-based cross-sectional study
Authors: Alemu Solomon Seyife , Hajure Mohammedamin , Agago Mahlet Tesfaye , Hussein Feisal , Gesisa Hana Israel , Teferi Sheleme Mengistu , Yohanes Daniel , Wedajo Lema Fikadu 
Published: June 2024

BackgroundOne of the main characteristics of the mental health condition known as burnout syndrome is an overwhelming feeling of physical and emotional tiredness, particularly with regard to one’s work. Midwives are the group most prone to burnout because they work in emergency situations to save two lives at a time, share the stress of laboring women, and put in extra hours without enough payment. Besides this, there is little information on burnout among Ethiopian midwives.ObjectivesTo assess burnout and associated factors among midwives working in public health facilities in West Arsi Zone, Ethiopia.Methods and materialsA census method cross-sectional study was conducted among all 467 midwives working in public health facilities found in the West Arsi Zone, Ethiopia, from September 1 and 30, 2023. A pretested, validated face-to-face interviewer-administered structured questionnaire was used to collect data. Then, binary logistic regression was used for analysis. Bi-variable and multivariable logistic regression analyses were employed to identify factors associated with burnout. The level of statistical significance was declared at p &lt; 0.05 with a 95% CI.ResultsOverall, the prevalence of burnout among midwives was 47.10% (95% CI: 42.55, 51.75%). Marital status not in union 2.03 (95% CI: 1.32–3.13), working more than 40 h per week 2.00 (95% CI: 1.29–3.08), conflict with their metron 2.33 (95% CI: 1.54–3.54), not satisfied with their current job 2.39 (95% CI: 1.56–3.66) and having depression symptoms 1.71 (95% CI: 1.06–2.74) were factors significantly associated with burnout.ConclusionThis study found that in the study area, almost half of the midwives experienced burnout. Thus, it is recommended that midwives should develop respectful interactions with both their mentors and colleagues. Secondly, we suggest that zonal health offices set up systems that by shortening working hours and boost job satisfaction by creating conducive working environment, provide opportunities for career advancement and increase employee engagement.