bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and computational characterization of ABCB11 and ABCG5 variants in Tunisian patients with neonatal/infantile low‐GGT intrahepatic cholestasis: Genetic diagnosis and genotype–phenotype correlation assessment
Authors: Khabou Boudour , Kallabi Fakhri , Abdelaziz Rim Ben , Maaloul Ines , Aloulou Hajer , Chehida Amel ben , Kammoun Thouraya , Barbu Veronique , Boudawara Tahya Sellami , Fakhfakh Faiza , Khemakhem Bassem , Sahnoun Olfa Siala 
Published: December 2023

AbstractMany inherited conditions cause hepatocellular cholestasis in infancy, including progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of diseases with highly overlapping symptoms. In our study, six unrelated Tunisian infants with PFIC suspicion were the subject of a panel–target sequencing followed by an exhaustive bioinformatic and modeling investigations. Results revealed five disease‐causative variants including known ones: (the p.Asp482Gly and p.Tyr354 * in the ABCB11 gene and the p.Arg446 * in the ABCC2 gene), a novel p.Ala98Cys variant in the ATP‐binding cassette subfamily G member 5 (ABCG5) gene and a first homozygous description of the p.Gln312His in the ABCB11 gene. The p.Gln312His disrupts the interaction pattern of the bile salt export pump as well as the flexibility of the second intracellular loop domain harboring this residue. As for the p.Ala98Cys, it modulates both the interactions within the first nucleotide‐binding domain of the bile transporter and its accessibility. Two additional potentially modifier variants in cholestasis‐associated genes were retained based on their pathogenicity (p.Gly758Val in the ABCC2 gene) and functionality (p.Asp19His in the ABCG8 gene). Molecular findings allowed a PFIC2 diagnosis in five patients and an unexpected diagnosis of sisterolemia in one case. The absence of genotype/phenotype correlation suggests the implication of environmental and epigenetic factors as well as modifier variants involved directly or indirectly in the bile composition, which could explain the cholestasis phenotypic variability.
Space use by African savannah elephants in an arid protected area dominated by a mosaic of different vegetation
Authors: Mukomberanwa Nobert Tafadzwa , Taru Phillip , Utete Beaven 
Published: December 2023

AbstractThe African savannah elephant (Loxodonta Africana) migrate in response to limiting environmental factors in arid areas. Using global positioning systems (GPS) telemetry data, we determined: (i) the dominant vegetation types used by African savannah elephants and (ii) the differences in the area occupied by dominant vegetation types in Gonarezhou National Park (GNP) in Zimbabwe. Significant spatiotemporal differences (p < 0.05) detected in vegetation types utilised by the African savannah elephant, and in the area covered by vegetation types induced a determinate foraging pattern. Global positioning system telemetry is a smart conservation tool for surveillance of movement patterns of African savannah elephants in protected areas.
Variation in clinical practice guideline recommendations for medication use in pregnancy in Australia: A systematic review
Authors: Cron Hayley T. , Simm Peter , Said Joanne M. , Cheong Jeanie L. Y. , Cranswick Noel , Hu Yanhong Jessika 
Published: December 2023

AbstractBackgroundMedication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent.AimsThis systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM).Materials and MethodsA literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.ResultsWe identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first‐line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed.ConclusionMultiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.
Climate change perception scale: Adaptation and psychometric properties in the Indonesian context
Authors: Adiwena Bartolomeus Yofana , Bramanwidyantari Maria 
Published: December 2023

AbstractOne of the crucial factors in changing behaviour towards pro‐environmental actions is climate change perception. The latest measurement tool for assessing this variable is the Climate Change Perception Scale (CCPS). However, CCPS has not gained widespread adoption and usage across different cultures, including Indonesia, and no analyses have been conducted to adapt and validate CCPS in the Indonesian context. Therefore, this study aimed to adapt, validate, and assess the measurement tool's consistency in Indonesia's cultural context. To investigate the instrument's psychometric properties, two studies (n = 358, 415) were conducted in Indonesia to provide evidence of the internal consistency, convergent validity, and predictive validity of CCPS. The results of a confirmatory factor analysis (CFA) showed that the Indonesian version of CCPS, which consists of 15 items, with three for each dimension, accurately and reliably measured perception of climate change. CCPS also demonstrated good convergent validity, as indicated by the significant correlations with a nature relatedness (r = 0.425, p < 0.01) and biospheric value (r = 0.341, p < 0.01) construct. Furthermore, it exhibited predictive validity by predicting pro‐environmental behaviour, β = 0.243, b = 0.176, t(413) = 5.10, p < 0.01. However, the Indonesian version of CCPS still needs to be tested and confirmed through various studies, considering the poor validity of the temporal dimension and the weak factor loading of the consequence dimension in Study 2.
Higher parental education was associated with good cognitive outcomes in infants with hypoxic‐ischaemic encephalopathy
Authors: Varga Zsuzsanna , Andorka Csilla , Pataki Margit , Meder Unoke , Szakmar Eniko , Szabo Attila J. , Szabo Miklos , Jermendy Agnes 
Published: December 2023

AbstractAimPredicting neurodevelopmental outcomes in hypoxic‐ischaemic encephalopathy (HIE) remains imprecise, despite advanced imaging and neurophysiological tests. We explored the predictive value of socio‐economic status (SES).MethodsThe cohort comprised 93 infants (59% male) with HIE, who had received therapeutic hypothermia. Patients underwent magnetic resonance imaging, and brain injuries were quantified using the Barkovich scoring system. Family SES was self‐reported using a questionnaire. Adverse outcomes were defined as mild to severely delayed development with a score of ≤85 in any domain at 2 years of age, based on the Bayley Scales of Infant Development, Second Edition. Data are presented as odds ratios (OR) with 95% confidence intervals (95% CI).ResultsMultiple regression modelling revealed that higher parental education was strongly associated with good cognitive development, when adjusted for gestational age, serum lactate and brain injuries (OR 2.20, 95% CI 1.16–4.36). The effect size of parental education (β = 0.786) was higher than one score for any brain injury using the Barkovich scoring system (β = −0.356). The literacy environment had a significant effect on cognitive development in the 21 infants who had brain injuries (OR 40, 95% CI 3.70–1352).ConclusionParental education and the literacy environment influenced cognitive outcomes in patients with HIE.
Looking beyond vaccines: Cultural tightness–looseness moderates the relationship between immunization coverage and disease prevention vigilance
Authors: Ma Mac Zewei , Chen Sylvia Xiaohua , Wang Xijing 
Published: December 2023

AbstractAdvancements in vaccination technologies mitigate disease transmission risks but may inadvertently suppress the behavioral immune system, an evolved disease avoidance mechanism. Applying behavioral immune system theory and utilizing robust big data analytics, we examined associations between rising vaccination coverage and government policies, public mobility, and online information seeking regarding disease precautions. We tested whether cultural tightness–looseness moderates the relationship between mass immunization and disease prevention vigilance. Comprehensive time series analyses were conducted using American data (Study 1) and international data (Study 2), employing transfer function modeling, cross‐correlation function analysis, and meta‐regression analysis. Across both the US and global analyses, as vaccination rates rose over time, government COVID‐19 restrictions significantly relaxed, community mobility increased, and online searches for prevention information declined. The relationship between higher vaccination rates and lower disease prevention vigilance was stronger in culturally looser contexts. Results provide initial evidence that mass immunization may be associated with attenuated sensitivity and enhanced flexibility of disease avoidance psychology and actions. However, cultural tightness–looseness significantly moderates this relationship, with tighter cultures displaying sustained vigilance amidst immunization upticks. These findings offer valuable perspectives to inform nuanced policymaking and public health strategies that balance prudent precautions against undue alarm when expanding vaccine coverage worldwide.
Protist symbionts of termites: diversity, distribution, and coevolution
Authors: Gile Gillian H. 
Published: December 2023

ABSTRACTThe symbiosis between termites and their hindgut protists is mutually obligate and vertically inherited. It was established by the late Jurassic in the cockroach ancestors of termites as they transitioned to wood feeding. Since then, protist symbionts have been transmitted from host generation to host generation by proctodeal trophallaxis (anal feeding). The protists belong to multiple lineages within the eukaryotic superphylum Metamonada. Most of these lineages have evolved large cells with complex morphology, unlike the non‐termite‐associated Metamonada. The species richness and taxonomic composition of symbiotic protist communities varies widely across termite lineages, especially within the deep‐branching clade Teletisoptera. In general, closely related termites tend to harbour closely related protists, and deep‐branching termites tend to harbour deep‐branching protists, reflecting their broad‐scale co‐diversification. A closer view, however, reveals a complex distribution of protist lineages across hosts. Some protist taxa are common, some are rare, some are widespread, and some are restricted to a single host family or genus. Some protist taxa can be found in only a few, distantly related, host species. Thus, the long history of co‐diversification in this symbiosis has been complicated by lineage‐specific loss of symbionts, transfer of symbionts from one host lineage to another, and by independent diversification of the symbionts relative to their hosts. This review aims to introduce the biology of this important symbiosis and serve as a gateway to the diversity and systematics literature for both termites and protists. A searchable database with all termite‐protist occurrence records and taxonomic references is provided as a supplementary file to encourage and facilitate new research in this field.
RUNX2‐related metaphyseal dysplasia with maxillary hypoplasia: A rare skeletal disorder resembling SFRP4‐related Pyle disease
Authors: Hordyjewska‐Kowalczyk Ewa , Wuyts Wim , Boeckx Nele , Verdonck An , Hendrickx Gretl , Mortier Geert 
Published: December 2023

AbstractMetaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra‐rare skeletal dysplasia caused by heterozygous intragenic RUNX2 duplications, comprising either exons 3 to 5 or exons 3 to 6 of RUNX2. In this study, we describe a 14‐year‐old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within RUNX2, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C‐terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders.
Conditional knockout of AIM2 in microglia ameliorates synaptic plasticity and spatial memory deficits in a mouse model of Alzheimer's disease
Authors: Ye Lei , Hu Mengsha , Mao Rui , Tan Yi , Sun Min , Jia Junqiu , Xu Siyi , Liu Yi , Zhu Xiaolei , Xu Yun , Bai Feng , Shu Shu 
Published: December 2023

AbstractAimsSynaptic dysfunction is a hallmark pathology of Alzheimer's disease (AD) and is strongly associated with cognitive impairment. Abnormal phagocytosis by the microglia is one of the main causes of synapse loss in AD. Previous studies have shown that the absence of melanoma 2 (AIM2) inflammasome activity is increased in the hippocampus of APP/PS1 mice, but the role of AIM2 in AD remains unclear.MethodsInjection of Aβ1‐42 into the bilateral hippocampal CA1 was used to mimic an AD mouse model (AD mice). C57BL/6 mice injected with AIM2 overexpression lentivirus and conditional knockout of microglial AIM2 mice were used to confirm the function of AIM2 in AD. Cognitive functions were assessed with novel object recognition and Morris water maze tests. The protein and mRNA expression levels were evaluated by western blotting, immunofluorescence staining, and qRT‐PCR. Synaptic structure and function were detected by Golgi staining and electrophysiology.ResultsThe expression level of AIM2 was increased in AD mice, and overexpression of AIM2 induced synaptic and cognitive impairments in C57BL/6 mice, similar to AD mice. Elevated expression levels of AIM2 occurred in microglia in AD mice. Conditional knockout of microglial AIM2 rescued cognitive and synaptic dysfunction in AD mice. Excessive microglial phagocytosis activity of synapses was decreased after knockout of microglial AIM2, which was associated with inhibiting complement activation.ConclusionOur results demonstrated that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease.
Efficacy of noiiglutide injection on body weight in obese Chinese adults without diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 2 trial
Authors: Li Yijun , Cheng Zhifeng , Lu Weiping , Li Ping , Jiang Hongwei , Yang Jing , Xu Jing , Zhang Cheng , Zhang Lili , Wang Yao , Bian Fang , Guo Weiying , Yu Xuefeng , Chen Xiaopan , Zhao Dong , Feng Bo , Qu Shen , Qin Jie , Zhang Yifei , Wang Lin , Chen Hong , Mu Yiming 
Published: December 2023

AbstractAimTo evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes.Materials and MethodsIn this 24‐week, randomized, double‐blind, placebo‐controlled phase 2 trial, 254 obese adults with a body mass index of 28.0‐40.0 kg/m2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24.ResultsAcross all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p‐values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%‐30.2%, 18.8%‐22.2%, 15.6%‐18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%).ConclusionsIn obese Chinese adults without diabetes, once‐daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders.
Anatomical and physiological consequences of beech leaf disease in Fagus grandifolia L.
Authors: Fletcher Leila R. , Borsuk Aleca M. , Fanton Ana C. , Johnson Kate M. , Richburg Jennifer , Zailaa Joseph , Brodersen Craig R. 
Published: December 2023

AbstractBeech leaf disease (BLD) is a foliar disease of American Beech (Fagus grandifolia L.) causally linked to the nematode Litylenchus crenatae mccannii and has rapidly spread throughout central and northeastern North America. This study aimed to characterize the anatomical and physiological differences between asymptomatic and symptomatic leaves to provide evidence for a mechanistic link between abnormal leaf development associated with BLD and the long‐term decline of affected trees. We found that leaf mass per area (LMA) and leaf thickness were 45% and 249% higher in symptomatic regions, respectively. The difference in leaf thickness was largely attributable to the spongy mesophyll being 410% thicker in symptomatic as compared with asymptomatic regions of the leaves, but palisade mesophyll and abaxial epidermal tissues were also thicker in symptomatic regions. While major vein density was not significantly different, minor vein density was significantly lower in symptomatic regions, suggesting that the effects on leaf development occur after the formation and initial development of first‐ and second‐order veins. Stomatal density was also lower in symptomatic leaves. Maximum photosynthetic rates were approximately 61% lower in symptomatic leaves and respiration rate increased as the percentage of affected leaf tissue increased. Collectively, our data show reduced photosynthetic capacity, increased respiration rates, and higher leaf construction costs, which will likely have a negative, long‐term impact on the carbon balance of trees affected by BLD.
Overexpression of SESN1 improves mitochondrial damage and mitophagy, a potential therapeutic strategy for cognitive dysfunction after anaesthesia
Authors: Sun Li , Hong Xiaoya , Wang Daliang , Li Yangyang 
Published: December 2023

AbstractPostoperative cognitive dysfunction (POCD) is a prevalent central nervous system complication predominantly observed in elderly patients. Sevoflurane, a general anaesthetic agent, has been implicated in the development of POCD, yet the underlying regulatory mechanisms potentially involving Sestrin1 (SESN1), a stress‐responsive protein that plays a critical role in cellular homeostasis and protection against stress‐induced damage, including oxidative stress and DNA damage, remain elusive. This study endeavoured to elucidate the impact of SESN1 on sevoflurane‐induced cognitive impairment in rats. Employing a model in which SESN1 was transfected into SD male rats and cognitive dysfunction was induced by sevoflurane. The Morris Water Maze test was used for behavioural evaluation, Enzyme‐Linked Immunosorbent Assay, Western blotting and immunofluorescence were applied to assess the influence of SESN1 on the inflammatory response and mitophagy in the rat hippocampus. The study further aimed to uncover the putative mechanism by which SESN1, through SIRT1, might modulate cognitive function. Concurrently, levels of malondialdehyde, superoxide dismutase and mitochondrially produced ATP within the rat hippocampus were quantified. Experimental outcomes suggested that SESN1 overexpression significantly mitigated the deleterious effects of sevoflurane anaesthesia, ameliorated neuroinflammation and inflammasome activation, modified mitochondrial function and facilitated mitophagy. Additionally, SESN1, via the activation of SIRT1, may suppress inflammasome activation and mitochondrial dysfunction. Collectively, these findings underscore SESN1's integral role in counteracting sevoflurane‐induced cognitive impairment, impeding inflammasome activation, enhancing mitochondrial function and fostering mitophagy, which appear to be intricately linked to SESN1‐mediated SIRT1 activation. SESN1 is a novel therapeutic target for POCD, potentially advancing neuroprotective strategies in clinical settings.
Aberrant morphometric networks in Alzheimer's disease have hemispheric asymmetry and age dependence
Authors: Maruoka Hiroyuki , Hattori Takaaki , Hase Takeshi , Takahashi Kunihiko , Ohara Masahiro , Orimo Satoshi , Yokota Takanori 
Published: December 2023

AbstractAlzheimer's disease (AD) is associated with abnormal accumulations of hyperphosphorylated tau and amyloid‐β proteins, resulting in unique patterns of atrophy in the brain. We aimed to elucidate some characteristics of the AD's morphometric networks constructed by associating different morphometric features among brain areas and evaluating their relationship to Mini‐Mental State Examination total score and age. Three‐dimensional T1‐weighted (3DT1) image data scanned by the same 1.5T magnetic resonance imaging (MRI) were obtained from 62 AD patients and 41 healthy controls (HCs) and were analysed by using FreeSurfer. The associations of the extracted six morphometric features between regions were estimated by correlation coefficients. The global and local graph theoretical measures for this network were evaluated. Associations between graph theoretical measures and age, sex and cognition were evaluated by multiple regression analysis in each group. Global measures of integration: global efficiency and mean information centrality were significantly higher in AD patients. Local measures of integration: node global efficiency and information centrality were significantly higher in the entorhinal cortex, fusiform gyrus and posterior cingulate cortex of AD patients but only in the left hemisphere. All global measures were correlated with age in AD patients but not in HCs. The information centrality was associated with age in AD's broad brain regions. Our results showed that altered morphometric networks due to AD are left‐hemisphere dominant, suggesting that AD pathogenesis has a left–right asymmetry. Ageing has a unique impact on the morphometric networks in AD patients. The information centrality is a sensitive graph theoretical measure to detect this association.