bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific associations between diabetes and dementia: the role of age at onset of disease, insulin use and complications
Authors: Zhou Chunmiao , Dong Caiyun , Xie Ziwei , Hao Wenting , Fu Chunying , Sun Huizi , Zhu Dongshan 
Published: February 2023

Abstract
Background
Whether the association of type 2 diabetes (T2DM) with dementia was differed by sex remains unclear, and the roles of age at onset of disease, insulin use and diabetes’ complications in their association are unknown.

Methods
This study analyzed data of 447 931 participants from the UK Biobank. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between T2DM and incident dementia [all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD)]. The roles of age at onset of disease, insulin use and diabetes’ complications in their association were also analyzed.

Results
Compared to people with no diabetes at all, people with T2DM had increased risk of all-cause dementia (HR 2.85, 95% CI 2.56–3.17). The HRs between T2DM and AD were higher in women than men, with an RHR (95%CI) of 1.56 (1.20, 2.02). There was a trend that people who experienced T2DM before age 55 had higher risk of VD than those who had T2DM after age 55. In addition, there was a trend that T2DM had higher effect on VD that occurred before age 75 years than events that occurred after age 75. Patients with T2DM using insulin had higher risk of all-cause dementia than those without insulin, with an RHR (95%CI) of 1.54 (1.00–2.37). People with complications had doubled risk of all-cause dementia, AD and VD.

Conclusions
Adopting a sex-sensitive strategy to address the risk of dementia in patients with T2DM is instrumental for a precision medicine approach. Meanwhile, it is warranted to consider patients' age at onset of T2DM, insulin use status and complications conditions.
Investigation of autism-related transcription factors underlying sex differences in the effects of bisphenol A on transcriptome profiles and synaptogenesis in the offspring hippocampus
Authors: Thongkorn Surangrat , Kanlayaprasit Songphon , Kasitipradit Kasidit , Lertpeerapan Pattanachat , Panjabud Pawinee , Hu Valerie W. , Jindatip Depicha , Sarachana Tewarit 
Published: February 2023

Abstract
Background
Bisphenol A (BPA) has been linked to susceptibility to autism spectrum disorder (ASD). Our recent studies have shown that prenatal BPA exposure disrupted ASD-related gene expression in the hippocampus, neurological functions, and behaviors associated with ASD in a sex-specific pattern. However, the molecular mechanisms underlying the effects of BPA are still unclear.

Methods
Transcriptome data mining and molecular docking analyses were performed to identify ASD-related transcription factors (TFs) and their target genes underlying the sex-specific effects of prenatal BPA exposure. Gene ontology analysis was conducted to predict biological functions associated with these genes. The expression levels of ASD-related TFs and targets in the hippocampus of rat pups prenatally exposed to BPA were measured using qRT-PCR analysis. The role of the androgen receptor (AR) in BPA-mediated regulation of ASD candidate genes was investigated using a human neuronal cell line stably transfected with AR-expression or control plasmid. Synaptogenesis, which is a function associated with genes transcriptionally regulated by ASD-related TFs, was assessed using primary hippocampal neurons isolated from male and female rat pups prenatally exposed to BPA.

Results
We found that there was a sex difference in ASD-related TFs underlying the effects of prenatal BPA exposure on the transcriptome profiles of the offspring hippocampus. In addition to the known BPA targets AR and ESR1, BPA could directly interact with novel targets (i.e., KDM5B, SMAD4, and TCF7L2). The targets of these TFs were also associated with ASD. Prenatal BPA exposure disrupted the expression of ASD-related TFs and targets in the offspring hippocampus in a sex-dependent manner. Moreover, AR was involved in the BPA-mediated dysregulation of AUTS2, KMT2C, and SMARCC2. Prenatal BPA exposure altered synaptogenesis by increasing synaptic protein levels in males but not in females, but the number of excitatory synapses was increased in female primary neurons only.

Conclusions
Our findings suggest that AR and other ASD-related TFs are involved in sex differences in the effects of prenatal BPA exposure on transcriptome profiles and synaptogenesis in the offspring hippocampus. These TFs may play an essential role in an increased ASD susceptibility associated with endocrine-disrupting chemicals, particularly BPA, and the male bias of ASD.
Association of systolic, diastolic, mean, and pulse pressure with morbidity and mortality in septic ICU patients: a nationwide observational study
Authors: Khanna Ashish K. , Kinoshita Takahiro , Natarajan Annamalai , Schwager Emma , Linn Dustin D. , Dong Junzi , Ghosh Erina , Vicario Francesco , Maheshwari Kamal 
Published: February 2023

Abstract
Background
Intensivists target different blood pressure component values to manage intensive care unit (ICU) patients with sepsis. We aimed to evaluate the relationship between individual blood pressure components and organ dysfunction in critically ill septic patients.

Methods
In this retrospective observational study, we evaluated 77,328 septic patients in 364 ICUs in the eICU Research Institute database. Primary exposure was the lowest cumulative value of each component; mean, systolic, diastolic, and pulse pressure, sustained for at least 120 min during ICU stay. Primary outcome was ICU mortality and secondary outcomes were composite outcomes of acute kidney injury or death and myocardial injury or death during ICU stay. Multivariable logistic regression spline and threshold regression adjusting for potential confounders were conducted to evaluate associations between exposures and outcomes. Sensitivity analysis was conducted in 4211 patients with septic shock.

Results
Lower values of all blood pressures components were associated with a higher risk of ICU mortality. Estimated change-points for the risk of ICU mortality were 69 mmHg for mean, 100 mmHg for systolic, 60 mmHg for diastolic, and 57 mmHg for pulse pressure. The strength of association between blood pressure components and ICU mortality as determined by slopes of threshold regression were mean (− 0.13), systolic (− 0.11), diastolic (− 0.09), and pulse pressure (− 0.05). Equivalent non-linear associations between blood pressure components and ICU mortality were confirmed in septic shock patients. We observed a similar relationship between blood pressure components and secondary outcomes.

Conclusion
Blood pressure component association with ICU mortality is the strongest for mean followed by systolic, diastolic, and weakest for pulse pressure. Critical care teams should continue to follow MAP-based resuscitation, though exploratory analysis focusing on blood pressure components in different sepsis phenotypes in critically ill ICU patients is needed.
Leukemogenic SHP2 mutations lead to erythropoietin independency of HCD-57 cells: a novel model for preclinical research of SHP2-mutant JMML
Authors: Zhao Yuming , He Chunxiao , Zhang Dengyang , Guo Yao , Peng Zhiyong , Yu Liuting , Li Na , Chen Chun , Zhao Zhizhuang Joe , Chen Yun 
Published: February 2023

AbstractLeukemogenic SHP2 mutations occur in 35% of patients with juvenile myelomonocytic leukemia (JMML), a rare but fatal hematopoietic malignancy without representative cell models, which are urgently needed to investigate the pathogenesis and to develop novel therapeutic strategies. In this study, we established stable cell lines with aberrant signaling resembling SHP2-mutant JMML through retroviral expression of SHP2-D61Y/E76K in HCD-57 cells, a murine erythroleukemia cell line that depends on erythropoietin (EPO) for survival. SHP2-D61Y/E76K drives the survival and proliferation of HCD-57 cells in the absence of EPO, but not in Ba/F3 cells in the absence of IL-3. Transformed HCD-57 cells showed activated MAPK signaling that is consistent with SHP2-mutant JMML. Transformed HCD-57 cells were sensitive to dasatinib and trametinib, two targeted drugs previously reported to inhibit SHP2-mutant JMML cells. Furthermore, we injected mutant SHP2-transformed HCD-57 cells into immune-deficient mice intravenously and found that these cells rapidly proliferated in the spleen and bone marrow, providing an excellent model for in vivo testing of drugs targeting the aberrant signaling of mutant SHP2. In conclusion, we established the novel cell lines HCD-57/SHP2-E76K and -D61Y that depended on signaling of mutant SHP2 for survival, thus resembling SHP2-mutant JMML. Our model is a valuable tool to investigate the pathogenic mechanisms of mutant SHP2 and targeted drugs for SHP2-mutant JMML.
The relationship between self-control and symptoms of anxiety and depression in patients with eating disorders: a cross-sectional study including exploratory longitudinal data
Authors: Eriksson Emmi , Ramklint Mia , Wolf-Arehult Martina , Isaksson Martina 
Published: February 2023

Abstract
Background
Personality style can partly be described as the way an individual controls and regulates emotions and can be divided into over- and undercontrol. Studies have indicated that personality style may impact the onset, clinical presentation, and recovery from an eating disorder (ED). Furthermore, symptoms of anxiety and depression are common in patients with EDs. However, the association between self-control levels and anxiety/depression symptoms in patients with EDs remains unknown. The main aim of this study was to assess how levels of self-control relate to anxiety/depression symptoms in patients with EDs, with a secondary, exploratory aim to assess the stability of self-control during treatment.

Methods
Patients were recruited from the outpatient ED clinic at the Uppsala University Hospital, between October 2014 and December 2019. In total, 227 patients (age: 25.4, SD: 7.1) were included at the start of their treatment, with 14 participants also completing post-treatment measurements. Self-control was assessed with the Ego Undercontrol scale (EUC-13), anxiety/depression symptoms with the Hopkins Symptoms Checklist (HSCL-25), and ED diagnosis and symptoms with the Eating Disorder Examination Interview (EDE-I) and Questionnaire (EDE-Q), respectively.

Results
A quadratic regression (n = 227) showed that levels of self-control accounted for about four percent of the variance in degree of global anxiety/depressive symptoms. Anxiety/depression symptoms were better explained by ED symptoms (R2 = 0.24). Visualizations in boxplots revealed a tendency for extreme values of both over- and undercontrol to be associated with higher levels of depression, whereas symptoms of anxiety increased with increasing undercontrol. In the exploratory analyses (n = 14) levels of self-control remained more stable than symptoms of anxiety and depression, which decreased significantly during ED treatment.

Conclusions
Our results indicated that anxiety/depression symptoms, in patients with EDs, were not strongly correlated with levels of self-control, but rather with ED symptoms. However, extreme values of both over- and undercontrol showed a tendency to be associated with higher levels of depression symptoms, whereas anxiety symptoms increased with increasing levels of undercontrol. Future studies could benefit from considering both over- and undercontrol as potentially dysfunctional.
Attachment and need to belong as moderators of the relationship between thwarted belongingness and suicidal ideation
Authors: Dienst Franziska , Forkmann Thomas , Schreiber Dajana , Höller Inken 
Published: February 2023

Abstract
Background
In the Interpersonal Theory of Suicide, thwarted belongingness is presented as a main predictor for suicidal ideation. Studies only partially support this prediction. The aim of this study was to examine whether the heterogenous results are due to moderating effects of attachment and the need to belong on the association between thwarted belongingness and suicidal ideation.

Methods
Four hundred forty-five participants (75% female) from a community sample aged 18 to 73 (M = 29.90, SD = 11.64) filled out online questionnaires about romantic attachment, their need to belong, thwarted belongingness, and suicidal ideation cross-sectionally. Correlations and moderated regression analyses were conducted.

Results
The need to belong significantly moderated the relationship between thwarted belongingness and suicidal ideation and was associated with higher levels of anxious attachment and avoidant attachment. Both attachment dimensions were significant moderators of the relationship between thwarted belongingness and suicidal ideation.

Conclusion
Anxious and avoidant attachment as well as a high need to belong are risk factors for suicidal ideation in people with thwarted belongingness. Therefore, attachment style and need to belong should both be considered in suicide risk assessment and therapy.
Portfolio vs. summative assessment: impacts on EFL learners’ writing complexity, accuracy, and fluency (CAF); self-efficacy; learning anxiety; and autonomy
Authors: Al-Hawamdeh Basem Okleh Salameh , Hussen Negash , Abdelrasheed Nasser Said Gomaa 
Published: February 2023

AbstractDue to the benefits of e-portfolio assessment and summative assessment in Ethiopia and a dearth of research, this study attempted to contrast e-portfolio assessment and summative assessment use in developing Ethiopian EFL learners’ writing complexity, accuracy, and fluency (CAF); learners’ autonomy; learning anxiety; and self-efficacy as they have not been investigated in Ethiopia. In order to accomplish these goals, 60 Ethiopian intermediate EFL students were selected according to their OQPT performance. E-portfolio served as the experimental group (EG), and summative functioned as the control group (CG). Writing CAF, self-efficacy, autonomy, and anxiety pretests were administered to both groups. Then, groups received different treatments. Writing CAF, self-efficacy, autonomy, and anxiety posttests were then given to the groups after the instruction period of 21 sessions. The collected data were examined using SPSS software. Then, independent samples t-tests and paired samples t-tests were run to assess the effects of the assessments on the learners’ writing CAF, autonomy, anxiety, and self-efficacy. The outcomes displayed that the experimental group and control group differed in performance. Actually, the e-portfolio assessment group outdid the summative assessment group. The e-portfolio assessment was found to be a more useful method for fostering learner autonomy, self-efficacy, and the writing CAF in EFL learners than summative assessment. Some recommendations, implications, and limitations were also listed at the end.
Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla
Authors: Tessier Aude , Roux Nathalie , Boutaud Lucile , Lunel Elodie , Hakkakian Leila , Parisot Mélanie , Garfa-Traoré Meriem , Ichkou Amale , Elkhartoufi Nadia , Bole Christine , Nitschke Patrick , Amiel Jeanne , Martinovic Jelena , Encha-Razavi Férechté , Attié-Bitach Tania , Thomas Sophie 
Published: February 2023

AbstractCongenital hydrocephalus is a common condition caused by the accumulation of cerebrospinal fluid in the ventricular system. Four major genes are currently known to be causally involved in hydrocephalus, either isolated or as a common clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. Here, we report 3 cases from 2 families with congenital hydrocephalus due to bi-allelic variations in CRB2, a gene previously reported to cause nephrotic syndrome, variably associated with hydrocephalus. While 2 cases presented with renal cysts, one case presented with isolated hydrocephalus. Neurohistopathological analysis allowed us to demonstrate that, contrary to what was previously proposed, the pathological mechanisms underlying hydrocephalus secondary to CRB2 variations are not due to stenosis but to atresia of both Sylvius Aqueduct and central medullar canal. While CRB2 has been largely shown crucial for apico-basal polarity, immunolabelling experiments in our fetal cases showed normal localization and level of PAR complex components (PKCι and PKCζ) as well as of tight (ZO-1) and adherens (β-catenin and N-Cadherin) junction molecules indicating a priori normal apicobasal polarity and cell–cell adhesion of the ventricular epithelium suggesting another pathological mechanism. Interestingly, atresia but not stenosis of Sylvius aqueduct was also described in cases with variations in MPDZ and CCDC88C encoding proteins previously linked functionally to the Crumbs (CRB) polarity complex, and all 3 being more recently involved in apical constriction, a process crucial for the formation of the central medullar canal. Overall, our findings argue for a common mechanism of CRB2, MPDZ and CCDC88C variations that might lead to abnormal apical constriction of the ventricular cells of the neural tube that will form the ependymal cells lining the definitive central canal of the medulla. Our study thus highlights that hydrocephalus related to CRB2, MPDZ and CCDC88C constitutes a separate pathogenic group of congenital non-communicating hydrocephalus with atresia of both Sylvius aqueduct and central canal of the medulla.
A modern multimodal pain protocol eliminates the need for opioids for most patients following total knee arthroplasty: results from a retrospective comparative cohort study
Authors: van Deventer Leland , Bronstone Amy , Leonardi Claudia , Bennett Matthew , Yager Peter , Dasa Vinod 
Published: February 2023

AbstractPurposeModern multimodal analgesia has been shown to significantly reduce opioid use following total knee arthroplasty (TKA). This study was conducted to determine if changing TKA discharge opioid prescriptions from automatic to upon request resulted in more opioid free recoveries without compromising pain control.MethodsBetween December 2019 and August 2021, an orthopedic surgeon performed 144 primary unilateral TKAs; patients received the same multimodal analgesia protocol except for postoperative opioid prescribing. The first consecutively‐treated cohort automatically received an opioid prescription following discharge (automatic group) and the second cohort received opioid prescriptions only upon request (upon request group). Opioid prescription data were derived from a prescription monitoring program and patient‐reported outcomes (PROs) were collected preoperatively and at 2 and 12 weeks postoperatively.ResultsA higher percentage of the upon request group was opioid free 3 months after TKA compared with the automatic group (55.6% vs 4.3%, p < 0.0001) without compromising pain or function. Among opioid‐naïve patients, 72% in the upon request group were opioid free after TKA compared with 5.4% in the automatic group. Opioid prescribing was not significantly reduced among opioid‐experienced patients regardless of the pain protocol.ConclusionRequiring patients to request opioid prescriptions following TKA resulted in a higher rate of opioid free TKA, especially among opioid‐naïve patients, without increasing pain compared with offering all patients an initial opioid prescription.Level of evidenceLevel III.
Ventral hernia repair with enhanced-view totally extraperitoneal technique after a massive weight loss by laparoscopic sleeve gastrectomy
Authors: Amiki Manabu , Ishiyama Yasuhiro , Mochizuki Ichitaro , Narita Kazuhiro , Goto Manabu , Sekikawa Koji 
Published: February 2023

Abstract
Background
Ventral hernia repair (VHR) for obese patients is often associated with an increased risk of postoperative complications and hernia recurrences. Achieving preoperative weight loss is ideal before VHR; however, it is difficult to attain with medical treatment. Metabolic and bariatric surgery (MBS) offers the most effective and durable treatment for obesity. Therefore, massive weight loss occurring after MBS will improve the outcome of VHR.

Case presentation
A 49-year-old man (122.9 kg, BMI 39.1 kg/m2) presented to our hospital wishing to undergo laparoscopic sleeve gastrectomy and VHR. Physical examination revealed a tennis ball-sized lower midline defect. Computed tomography (CT) scans revealed a hernia orifice 5 cm in width and 10 cm in height. As the hernia orifice was large, mesh reinforcement was essential. We planned for him to undergo VHR after massive weight loss was achieved by MBS. VHR was performed using the enhanced-view totally extraperitoneal (eTEP) technique after weight loss of 38 kg was achieved 9 months following laparoscopic sleeve gastrectomy. His postoperative course was uneventful, and neither recurrence nor seroma was observed at 1 year follow-up.

Conclusions
eTEP repair of a ventral hernia after massive weight loss following MBS would appear to be the best combination treatment for obese patients with ventral hernias. However, long-term follow-up is necessary to establish its safety and efficacy.
The factors influencing inappropriate child feeding practices among families receiving nutrition allowance in the Himalayan region of Nepal
Authors: Sunuwar Dev Ram , Bhatta Anuradha , Rai Anjana , Chaudhary Narendra Kumar , Tamang Man Kumar , Nayaju Suvash , Singh Devendra Raj 
Published: February 2023

Abstract
Background
Child feeding practices during the first two years of life are crucial to ensure good health and nutrition status. This study aimed to assess the factors influencing inappropriate child feeding practices in children aged 6 − 23 months in families receiving nutrition allowance in the remote Mugu district, Nepal.

Methods
A community-based cross-sectional study was conducted among 318 mothers who had children aged 6 − 23 months of age in the seven randomly selected wards. Systematic random sampling technique was used to select the desired number of respondents. Data were collected using pre-tested semi-structured questionnaire. Bivariate and multivariable binary logistic regression was used to estimate crude odds ratio (cOR), and adjusted odds ratio (aOR), and 95% confidence intervals (CIs) to understand factor associated with child feeding practices.

Results
Almost half of the children aged 6 − 23 months were not consuming a diverse diet (47.2%; 95% CI: 41.7%, 52.7%), did not meet the recommended minimum meal frequency (46.9%; 95% CI: 41.4%, 52.4%) and did not consume minimum acceptable diet (51.7%; 95% CI: 46.1%, 57.1%). Only 27.4% (95% CI: 22.7%, 32.5%) of children met the recommended complementary feeding practices. Multivariable analysis showed maternal characteristics such as mothers who gave birth at home (aOR = 4.70; 95% CI: 1.03, 21.31) and mothers in unpaid employment (aOR = 2.56; 95% CI: 1.06, 6.19) were associated with increased odds of inappropriate child feeding practices. Household economy (i.e. family with < 150 USD monthly income) was also associated with increased odds of inappropriate child feeding practices (aOR = 1.19; 95% CI: 1.05, 2.42).

Conclusion
Despite the receipt of nutritional allowances, child feeding practices among 6 − 23 months children were not optimal. Additional context-specific behavior change strategies on child nutrition targeting mothers may be required.