bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: exome sequencing identified mutations in the LRP5 and LGR4 genes in a case of osteoporosis with recurrent fractures and extraskeletal manifestations
Authors: Mehta Poonam , Sharma Aakriti , Goswami Anupam , Gupta Sushil Kumar , Singhal Vaibhav , Srivastava Kinshuk Raj , Chattopadhyay Naibedya , Singh Rajender 
Published: October 2024

BackgroundGenetic mutations have been reported in a number of bone disorders with or without extra-skeletal manifestations. The purpose of the present study was to investigate the genetic cause in a middle-aged woman with osteoporosis, recurrent fractures and extraskeletal manifestations.MethodsA 56-year-old Indian woman presented to the clinic with complaints of difficulty in walking, recurrent fractures, limb bending, progressive skeletal deformities, and poor overall health. At the age of 37, she had experienced severe anemia with diarrhea, significant weight loss, knuckle pigmentation, and a significant loss of scalp hair. She had received multiple blood transfusions and parenteral iron supplementation with normalization of hemoglobin. Subsequently, she had premature menopause at the age of 37. She died at the age of 61 due to liver failure. Exome sequencing followed by Sanger sequencing were undertaken to identify the potential pathogenic mutations.ResultsGenetic investigation identified likely pathogenic mutations in the LRP5 and LGR4 genes. Out of the two mutations, the heterozygous mutation (c.1199C&gt;T) in the LRP5 gene resulted in a non-synonymous substitution of alanine with valine at the 400th position, and the second mutation (c.1403A&gt;C) in the LGR4 gene led to a non-synonymous substitution of tyrosine with serine at the 468th residue of the protein. The minor allele frequencies of the c.1199C&gt;T (LRP5) substitution in the 1000 genomes and IndiGenomes databases are 0.0003 and 0.001, while the c.1403A&gt;C (LGR4) substitution has not been reported in these databases. Various in silico prediction tools suggested LGR4 mutation to be pathogenic and LRP5 mutation to be likely pathogenic.ConclusionHeterozygous mutations in the LRP5 and LGR4 genes had additive deteriorative effects on BMD, resulting in recurrent fractures and bone deformities, and extended the effect to extraskeletal sites, contributing to the poor overall health in this patient.
Evolution of the ecological security pattern of the Yellow River Basin based on ecosystem services: a case study of the Shanxi section, China
Authors: Wang Jinfang , Lv Zhihong , Zhen Zhilei , Wu Qian 
Published: October 2024

Identifying and evaluating the ecological security pattern (ESP) of region can provide a solid foundation for optimizing regional ecosystem elements and improving regional ecological security. The PLUS model, InVEST model, and circuit theory were used to analyze the ecosystem services and ESP of the Shanxi section of the Yellow River Basin (SYRB) between 2005 and 2035. The findings revealed that 1) The total area of land use shift across categories between 2005 and 2020 was 6,080.99 km2, or 5.22% of the SYRB’s total area. Under the natural development scenario, the total land transfer area from 2020 to 2035 was predicted to be 4,605.10 km2. Among these, the tendency for construction and forest land was expanding, while the tendency for cultivated land, grassland, water area, and unused land was shrinking; 2) From 2005 to 2035, the SYRB’s water yield and soil conservation all decreased, while the habitat quality and carbon storage showed a declining tendency; 3) The ecological source increased from 35,767.00 km2 in 2005 to 39,931.00 km2 in 2035; the total length of the ecological corridors expanded from 2,792.24 km to 3,553.18 km between 2005 and 2035; the ecological pinch points increased from 27 in 2005 to 40 in 2035; the ecological barrier points increased from 21 in 2005 to 28 in 2035, which show that the ESP remained unstable; 4) According to the ecosystem service characteristics of the SYRB in 2020, an ESP of “one axis, two zones, four corridors, and multiple points” was constructed. This study could provide useful guidance for improving the spatial pattern of land use and maintaining ecosystem services.
Determinants of micronutrient supplementation during pregnancy among women in three sub-Saharan African countries: a multilevel logistic regression model
Authors: Mekonen Enyew Getaneh , Zegeye Alebachew Ferede , Workneh Belayneh Shetie , Ali Mohammed Seid , Gonete Almaz Tefera , Alemu Tewodros Getaneh , Tamir Tadesse Tarik , Tekeba Berhan , Wassie Mulugeta , Kassie Alemneh Tadesse 
Published: October 2024

BackgroundPoor maternal nutrition during pregnancy is a common cause of poor maternal and infant outcomes. Micronutrient deficiencies are common among pregnant women in low- and middle-income countries, including sub-Saharan Africa. Pregnant women are recommended to take micronutrients like iron or folic acid and deworming medication during pregnancy. Therefore, this study was conducted to assess micronutrient intake and its associated factors among pregnant women in three countries using the most recent demographic and health survey.MethodsWe used data from the most recent demographic and health surveys, which were carried out between 2019 and 2022 in three sub-Saharan African countries. The study included a weighted sample of 13,568 reproductive-age women who had given birth within the five years prior to the survey. Utilizing multilevel logistic regression, the factors associated with the dependent variable were identified. Model comparison and fitness were assessed using the deviance (-2LLR), likelihood ratio test, median odds ratio, and intra-class correlation coefficient. Ultimately, factors were deemed statistically significant if they had a p-value less than 0.05.ResultsThe pooled prevalence of micronutrient intake among pregnant women during pregnancy of last birth was 77.56% (95% CI: 76.85%–78.25%). Factors like age [AOR = 1.78; 95% CI (1.14, 2.77)], educational status [AOR = 1.49; 95% CI (1.23, 1.79)], marital status [AOR = 0.66; 95% CI (0.58, 0.75)], working status [AOR = 1.17; 95% CI (1.01, 1.34)], media exposure [AOR = 1.20; 95% CI (1.05, 1.38)], preceding birth interval [AOR = 1.17; 95% CI (1.01, 1.34)], number of ANC visits [AOR = 1.65; 95% CI (1.29, 2.10)], and residence [AOR = 1.19; 95% CI (1.03, 1.37)] were significantly associated with micronutrient intake among pregnant women.ConclusionsMore than three-fourths of the study subjects were micronutrient supplemented during their pregnancy. Improving women's education, disseminating nutrition information through media, providing more attention to young pregnant women who live in rural areas, increasing the number of ANC visits, and women's empowerment are strongly recommended.
Epstein–Barr virus reactivation in pediatric allogeneic stem cell transplant recipients: an 11-year experience on viral load and B lymphocyte monitoring strategy
Authors: Ferrando Giulia , Bagnasco Francesca , Pierri Filomena , Pestarino Sara , Dell’Orso Gianluca , Giardino Stefano , Di Marco Eddi , Santaniello Maria , Castagnola Elio , Faraci Maura 
Published: October 2024

BackgroundEpstein–Barr virus (EBV) reactivation represents a frequent condition after allogeneic hematopoietic stem cell transplantation (allo-HCT) and can cause the development of a severe complication: post-transplant lymphoproliferative disease (PTLD). This retrospective study aims at investigating the incidence of EBV reactivations and analyzing the potential impact of recipient/donor-related transplant-related factors in pediatric patients. The secondary objective was to study the consequences of the approach used at our center regarding the initiation of pre-emptive therapy.MethodsThis study used a retrospective evaluation of patients aged ≤25 years who received an allo-HCT at IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Giannina Gaslini, between 2012 and 2022, with follow-up censored in July 2023. Criteria to start rituximab were as follows: a viral load ≥20,000 copies/105 PBMCs or ≥10,000/105 PBMCs associated with a rise in the proportion of CD 20+ lymphocytes.ResultsOverall, 214 allo-HCTs were performed in 189 patients. A total of 127 (59.3%) procedures were complicated by at least one EBV reactivation, but in only one rituximab was administered. All other reactivations were characterized by viremia below reference ranges and no increase in CD20+ lymphocytes, without clinical consequences. Risk factors for EBV reactivation identified were associated with delayed immune reconstitution.ConclusionThese results could suggest the effectiveness of the approach used in providing pre-emptive therapy. The strategy adopted differs from that highlighted by other studies and allowed the reduction of the number of children who received rituximab. It has proven effective considering the low incidence rate of PTLD and reduces the risk of rituximab-related adverse events.
Clinical pharmacist interventions in nutrition-and drug-related problems in critically ill patients with renal dysfunction: a non-randomized controlled study
Authors: Özgan Betül , Ayhan Yunus Emre , Apikoglu Sule , Karakurt Sait 
Published: October 2024

BackgroundCritically ill intensive care unit (ICU) patients often face life-threatening drug-related problems (DRPs) and malnutrition. Clinical pharmacists (CPs) play a crucial role in mitigating these issues and improving outcomes.AimThis study was designed to detect, prevent, reduce or resolve nutrition-related problems (NRPs) and DRPs in intensive care patients with renal dysfunction through clinical pharmacy services.MethodThis 9-month, prospective, non-randomized, controlled study was conducted in the ICU. During the intervention period (IP), CP recommendations addressing NRPs and DRPs were provided to the healthcare team. NRPs were evaluated using an expert-developed enteral nutrition consensus protocol, while DRPs were classified according to the Pharmaceutical Care Network Europe (PCNE) Classification for Drug-Related Problems Version 9.1.ResultsThe study included 60 patients with a median age of 73 years (IQR: 60.5–80). A total of 504 DRPs (8.4 per patient) were identified across all patients. DRPs were decreased by 50% during the IP compared to the observation period (OP) (p &lt; 0.001). The most common causes of DRPs were ‘too low a drug dose’ (22.2%), ‘drug–drug interactions’ (17%), and ‘too high a drug dose’ (16.4%). Of the recommendations made to the prescribing physician, 140 (97.9%) were accepted. In the IP, targeted calorie and protein supplementation was fully achieved in more patients (p &lt; 0.05). The most common recommendations included ‘changes in the rate of nutrition’ (66.7%), ‘vitamin supplementation’ (16.7%), and ‘changes in enteral nutrition products’ (7.7%).ConclusionThis study highlights the high incidence of DRPs and malnutrition risk in ICU patients with renal dysfunction, emphasizing the vital role of clinical pharmacists. Their collaboration with healthcare professionals significantly reduced both DRPs and NRPs.
Use of esketamine for tracheoscopic drug injection: a randomized controlled trial
Authors: Zhao Xiaoming , Zhou Zhendong , Li Zhenhua , Hu Zhaolan , Yu Yuanyuan 
Published: October 2024

BackgroundSufentanil may induce hypotensive bradycardia and other adverse reactions in elderly patients during anesthesia, while esketamine exhibits sedative and analgesic effects with minimal impact on respiration and circulation. The objective of this study was to investigate the impact of these two anesthetics on vital signs in patients undergoing bronchoscopy and lavage under general anesthesia.MethodThis study was a randomized controlled trial with a parallel design. A total of 100 patients aged ≥60 years with ASAI or II who were undergoing bronchoscopy and lavage were randomly assigned to two groups: group A (esketamine, n = 50) and group B (sufentanil, n = 50). During anesthesia induction, both groups received intravenous infusion of propofol at a dose of 1.5 mL/kg and atracurium. In group A, esketamine at a dose of 0.3 mg/kg was injected; in group B, sufentanil at a dose of 0.2 μg/kg was injected intravenously. Subsequently, a laryngeal mask was inserted and connected to an anesthesia machine for mechanical ventilation. Anesthesia maintenance involved continuous intravenous infusion of propofol at a dose of 3 mL/kg. The mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO2) were recorded at various time points: before anesthesia injection (T0), after laryngeal mask insertion (T1), 5 min after the operation started (T2), 15 min after the operation started (T3), and before the end of the operation (T4). Additionally, the recovery time was recorded.ResultsThe blood pressure of patients in the esketamine group exhibited higher levels compared to those in the sufentanil group at multiple time points during the operation, while maintaining a more stable intraoperative blood pressure and shorter postoperative recovery time than that observed in the sufentanil group. The blood pressure and heart rate of patients in the esketamine group exhibited significant fluctuations after laryngeal mask implantation compared to pre-anesthesia induction, with a statistically significant increase observed. Conversely, no significant changes were observed in the sufentanil group. The heart rate and oxygen saturation showed no significant differences between the two groups, nor did the amount of propofol administered during the procedure.ConclusionThe utilization of esketamine during the induction phase of bronchoscopy and lavage under general anesthesia can enhance hemodynamic stability and reduce the occurrence of hypotension, thereby facilitating postoperative anesthetic recovery.
Metagenome-based characterization of the gut bacteriome, mycobiome, and virome in patients with chronic hepatitis B-related liver fibrosis
Authors: Chen Wenlin , Liang Fang , Zhang Yue , Zhang Yuncheng , Lv Jinzhen , Jin Xiande , Ran Yun , Li Shenghui , Sun Wen 
Published: October 2024

IntroductionThe gut microbiota is believed to be directly involved in the etiology and development of chronic liver diseases. However, the holistic characterization of the gut bacteriome, mycobiome, and virome in patients with chronic hepatitis B-related liver fibrosis (CHB-LF) remains unclear.MethodsIn this study, we analyzed the multi-kingdom gut microbiome (i.e., bacteriome, mycobiome, and virome) of 25 CHB-LF patients and 28 healthy individuals through whole-metagenome shotgun sequencing of their stool samples.ResultsWe found that the gut bacteriome, mycobiome, and virome of CHB-LF patients were fundamentally altered, characterized by a panel of 110 differentially abundant bacterial species, 16 differential fungal species, and 90 differential viruses. The representative CHB-LF-enriched bacteria included members of Blautia_A (e.g., B. wexlerae, B. massiliensis, and B. obeum), Dorea (e.g., D. longicatena and D. formicigenerans), Streptococcus, Erysipelatoclostridium, while some species of Bacteroides (e.g., B. finegoldii and B. thetaiotaomicron), Faecalibacterium (mainly F. prausnitzii), and Bacteroides_A (e.g., B. plebeius_A and B. coprophilus) were depleted in patients. Fungi such as Malassezia spp. (e.g., M. japonica and M. sympodialis), Candida spp. (e.g., C. parapsilosis), and Mucor circinelloides were more abundant in CHB-LF patients, while Mucor irregularis, Phialophoraverrucosa, Hortaea werneckii, and Aspergillus fumigatus were decreases. The CHB-LF-enriched viruses contained 18 Siphoviridae, 12 Myoviridae, and 1 Podoviridae viruses, while the control-enriched viruses included 16 Siphoviridae, 9 Myoviridae, 2 Quimbyviridae, and 1 Podoviridae_crAss-like members. Moreover, we revealed that the CHB-LF-associated gut multi-kingdom signatures were tightly interconnected, suggesting that they may act together on the disease. Finally, we showed that the microbial signatures were effective in discriminating the patients from healthy controls, suggesting the potential of gut microbiota in the prediction of CHB-LF and related diseases.DiscussionIn conclusion, our findings delineated the fecal bacteriome, mycobiome, and virome landscapes of the CHB-LF microbiota and provided biomarkers that will aid in future mechanistic and clinical intervention studies.
Mean global field power is reduced in infantile epileptic spasms syndrome after response to vigabatrin
Authors: Nair Arjun , Ewusie Joycelyne , Pentz Rowan , Whitney Robyn , Jones Kevin 
Published: October 2024

PurposeInfantile epileptic spasms syndrome (IESS) is associated with abnormal neuronal networks during a critical period of synaptogenesis and brain plasticity. Hypsarrhythmia is a visual EEG biomarker used to diagnose IESS, assess response to treatment, and monitor relapse. Computational EEG biomarkers hold promise in providing unbiased, reliable, and objective criteria for clinical management. We hypothesized that computational and visual EEG biomarkers of IESS would correlate after treatment with vigabatrin and that these responses might differ between responders and non-responders.MethodsA retrospective analysis was conducted at a single center, involving children with IESS at initial diagnosis and following first-line treatment with vigabatrin. Visual EEG biomarkers of hypsarrhythmia were compared with computational EEG biomarkers, including spike and spike fast-oscillation source coherence, spectral power, and mean global field power, using retrospective analysis of EEG recorded at initial diagnosis and after vigabatrin treatment. Responders and non-responders were compared based on the characteristics of their follow-up EEGs.ResultsIn this pilot study, we observed a reduction in the EEG biomarker of hypsarrhythmia/modified hypsarrhythmia from 20/20 (100%) cases at the initial diagnosis to 9/20 (45%) cases after treatment with vigabatrin, indicating a 55% (11/20) responder rate. No significant difference in spike frequency was observed after treatment (p = 0.104). We observed no significant differences after treatment with vigabatrin in the computational EEG biomarkers that we assessed, including spike source coherence at 90% (p = 0.983), spike source coherence lag range (p &gt; 0.999), spike gamma source coherence at 90% (p = 0.177), spike gamma source coherence lag range (p &gt; 0.999), spectral power (0.642), or mean global field power (0.932). However, when follow-up EEGs were compared, there was a significant difference in mean global field power (p = 0.038) between vigabatrin responders and non-responders. In contrast, no such difference was observed for spike source coherence at 90% (p = 0.285), spike course coherence lag range (p = 0.819), spike gamma source coherence at 90% (p = 0.205), spike gamma source coherence lag range (p &gt; 0.999), or spectral power (p = 0.445). Finally, our treated group did not differ significantly from healthy controls at initial diagnosis or follow-up in terms of spectral power (p = 0.420) or mean global field power (0.127).ConclusionIn this pilot study, we show that mean global field power is a computational EEG biomarker that is significantly reduced in IESS after treatment with vigabatrin. Although computational EEG biomarkers of network connectivity using spike source coherence appear to be a promising tool, future studies should further explore their potential for assessing treatment responses in IESS.
Weight status change during four years and left ventricular hypertrophy in Chinese children
Authors: Liu Qin , Li Cheng , Yang Lili , Gong Zhuo , Zhao Min , Bovet Pascal , Xi Bo 
Published: October 2024

ObjectiveIt is well-established that overweight/obesity is a major risk factor for left ventricular hypertrophy (LVH) in childhood. However, it is still unclear if reversing from overweight/obesity to normal weight is associated with decreased LVH in children. This study aimed to examine the association between weight status change during four years and LVH among Chinese children based on a prospective cohort study.MethodsData were obtained from the Huantai Childhood Cardiovascular Health Cohort Study in China. A total of 1,178 children without LVH at baseline (mean age: 8.3 years) were included in this study. According to weight status [normal weight or overweight (including obesity)] at baseline (2017) and follow-up (2021), children were divided, based on sex- and age-adjusted body mass index (BMI), into four groups: persistent normal weight (normal weight at both baseline and follow-up), incident overweight (normal weight at baseline but overweight at follow-up), reversal to normal weight (overweight at baseline but normal weight at follow-up), persistent overweight (overweight at both baseline and follow-up).ResultsAfter adjustment for potential confounding factors, children with incident overweight (n = 114, 30.63 ± 4.74 g/m2.7) and those with persistent overweight (n = 363, 31.56 ± 6.24 g/m2.7) had higher left ventricular mass index (LVMI) at the end of the follow-up period than those with persistent normal weight (n = 632, 28.46 ± 7.64 g/m2.7), while those who reversed from overweight to normal weight had a non-significantly lower LVMI (n = 69, 28.51 ± 4.28 g/m2.7). Compared to children with persistent normal weight, those with persistent overweight [odds ratio (OR) = 5.14, 95% confidence interval (CI) = 3.33–7.95] and those with incident overweight (OR = 3.34, 95% CI = 1.77–6.30) had an increased risk of LVH. The risk of LVH tended to decrease, although not significantly, in those who reversed from overweight to normal weight (OR = 0.76, 95% CI = 0.22–2.55).ConclusionOur findings demonstrate a positive association between overweight and left ventricular mass in children and suggest that LVH in childhood could be attenuated by weight loss.
Syntax and the brain: language evolution as the missing link(ing theory)?
Authors: Benítez-Burraco Antonio , Progovac Ljiljana 
Published: October 2024

IntroductionThis paper provides proof of concept that neurolinguistic research on human language syntax would benefit greatly by expanding its scope to include evolutionary considerations, as well as non-propositional functions of language, including naming/nicknaming and verbal aggression. In particular, an evolutionary approach can help circumvent the so-called granularity problem in studying the processing of syntax in the brain, that is, the apparent mismatch between the abstract postulates of syntax (e.g. Tense Phrase (TP), Determiner Phrase (DP), etc.) and the concrete units of neurobiology (neurons, axons, etc.).MethodsFirst, we decompose syntax into its evolutionary primitives, identifying one of the earliest stages as a simple, flat combination of just one verb and one noun. Next, we identify proxies (“living fossils”) of such a stage in present-day languages, including compounds and small clauses, lacking at least some layers of structure, e.g. TPs and DPs. These proxies of ancestral language have been subjected to fMRI neuroimaging experiments.ResultsWe discuss the finding that less hierarchical small clauses, in contrast to full sentences with TPs and DPs, show reduced activation in the left Broca’s area (BA) 44 and the right basal ganglia, consistent with the hypothesis that more recent, more elaborate syntax requires more connectivity in the Broca’s-basal ganglia network, whose neuronal density has been significantly enhanced in recent evolution, implicating mutations in FOXP2 and other genes. We also discuss the finding that the processing of ancestral verb-noun compounds, which are typically used for (derogatory) naming and nicknaming, shows enhanced activation in the right fusiform gyrus area (BA 37), the area that is implicated in the processing of metaphoricity and imageability, but also in naming and face recognition, opening up an intriguing possibility that the enhanced face recognition in humans was facilitated by the early emergence of a simple syntactic strategy for naming.DiscussionThe considerations in this paper are consistent with the hypothesis of a gradual gene-culture co-evolution of syntax and the brain, targeting cortico-striatal brain networks. It is also of note that a sound grounding in neurobiology of language should in turn inform syntactic theories themselves.