bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting CLDN6 in germ cell tumors by an antibody-drug-conjugate and studying therapy resistance of yolk-sac tumors to identify and screen specific therapeutic options
Authors: Skowron Margaretha A. , Kotthoff Mara , Bremmer Felix , Ruhnke Katja , Parmaksiz Fatma , Richter Annika , Küffer Stefan , Reuter-Jessen Kirsten , Pauls Stella , Stefanski Anja , Ströbel Philipp , Stühler Kai , Nettersheim Daniel
Published: March 2023

Background

Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST.

Methods

Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay.

Results

We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6+ GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance.

Conclusions

In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.
The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway
Authors: Yang Mei , Li Lin , Huang Xiaojie , Xing Hui , Hong Li , Jiang Chunfan
Published: March 2023

Background

Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the mechanisms mediated by abnormal methylation in the development of EMS.

Materials and methods

Next-generation sequencing dataset and methylation profiling dataset were used to screen out the key gene SFRP2. Western bolt, Real-time PCR, Aza-2?deoxycytidine treatment, luciferase reporter assay, Methylation-specific PCR , Bisulfite sequencing PCR and lentivirus infection were carried out to detect the methylation status and signaling pathway with the primary epithelial cells. Transwell assay and wound scratch assay were implemented to observe the differences of migration ability with the intervening with the expression of SFRP2.

Results

To define the role of the DNA methylation-regulated genes in the pathogenesis of EMS, we performed both DNA methylomic and expression analyses of ectopic endometrium and ectopic endometrium epithelial cells(EEECs) and found that SFRP2 is demethylated/upregulated in ectopic endometrium and EEECs. The expression of lentivirus carrying SFRP2 cDNA up-regulates the activity of Wnt signaling and the protein expression of ?-catenin in EEECs. SFRP2 impact on the invasion and migration of ectopic endometrium by modulating the activities of the Wnt/?-catenin signaling pathway. The invasion and migration ability of EEECs were significantly strengthened after demethylation treatment including 5-Aza and the knockdown of DNMT1.

Conclusion

In summary, the increased SFRP2 expression-induced Wnt/?-catenin signaling due to the demethylation of the SFRP2 promoter plays an important role in the pathogenesis of EMS, suggesting that SFRP2 might be a therapeutic target for EMS treatment.
Pinpointing the precise stimulation targets for brain rehabilitation in early-stage Parkinson’s disease
Authors: Lu Hanna , Li Jing , Zhang Li , Meng Lin , Ning Yuping , Jiang Tianzi
Published: March 2023

Background

Transcranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson’s disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients.

Objective

To investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients.

Methods

Structural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method.

Results

Early-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures.

Conclusion

SCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice.
Alleviating the adverse effects of salinity stress on Salicornia persica using sodium nitroprusside and potassium nitrate
Authors: Moghaddam Abbasali , Larijani Hamid Reza , Oveysi Meysam , Moghaddam Hamid Reza Tohidi , Nasri Mohammad
Published: March 2023

Background

Glasswort (Salicornia persica) is identified as a halophyte plant, which is one of the most tolerant plants to salt conditions. The seed oil of the plant contains about 33% oil. In the present study, the effects of sodium nitroprusside (SNP; 0, 0.1, 0.2, and 0.4 mM) and potassium nitrate (KNO3; 0, 0.5, and 1%) were evaluated on several characteristics of glasswort under salinity stress (0, 10, 20, and 40 dS/m).

Results

morphological features, phenological traits, and yield parameters such as plant height, number of days to flowering, seed oil, biological yield, and seed yield significantly decreased in response to severe salt stress. However, the plants needed an optimal salinity concentration (20 dS/m NaCl) to obtain high amounts of seed oil and seed yield. The results also showed that a high level of salinity (40 dS/m NaCl) caused a decrease in plant oil and yield. In addition, by increasing the exogenous application of SNP and KNO3, the seed oil and seed yield increased.

Conclusions

The application of SNP and KNO3were effective in protectingS. persicaplants from the deleterious effects of severe salt stress (40 dS/m NaCl), thereby restoring the activity of antioxidant enzymes, increasing the proline content, and maintaining cell membrane stability. It seems that both factors, i.e. SNP and KNO3, can be applied as mitigators of salt stress in plants.
Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study
Authors: Babahajiani Media , Zarepur Ehsan , Khosravi Alireza , Mohammadifard Noushin , Noohi Feridoun , Alikhasi Hasan , Nasirian Shima , Moezi Bady Seyed Ali , Janjani Parisa , Solati Kamal , Lotfizadeh Masoud , Ghaffari Samad , Javanmardi Elmira , Salari Arsalan , Gholipour Mahboobeh , Dehghani Mostafa , Cheraghi Mostafa , Assareh Ahmadreza , Haybar Habib , Namayandeh Seyedeh Mahdieh , Madadi Reza , Kojuri Javad , Mansourian Marjan , Sarrafzadegan Nizal
Published: March 2023

Background

Diverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD.

Methods

In this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients’ demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling.

Results

The mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04–1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40–3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05–3.67)).

Conclusions

This study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups.
Prolonged length of stay and its associated factors at adult emergency department in amhara region comprehensive specialized hospitals, northwest Ethiopia
Authors: Belayneh Asnake Gashaw , Temachu Yemataw Zewdu , Messelu Mengistu Abebe , Gebrie Mignote Hailu
Published: March 2023

Background

Prolonged length of stay at the emergency department interferes with the main goal of emergency care and results in adverse patient outcomes like nosocomial infection, dissatisfaction, morbidity, and mortality. Despite this, little is known about the length of stay and the factors that influence it in Ethiopia’s emergency department.

Methods

An institution-based cross-sectional study was conducted on 495 patients admitted at Amhara region comprehensive specialized hospitals emergency department from May 14 to June 15/2022. A systematic random sampling was employed to select study participants. A pretested structured interview-based questionnaire was used to collect data by using Kobo toolbox software. SPSS version 25 was used for data analysis. Bi-variable logistic regression analysis was carried out to select variables with P-value < 0.25. The significance of association was interpreted using an Adjusted Odds Ratio with a 95% confidence interval. Variables with P-value < 0.05 in the multivariable logistic regression analysis were inferred to be significantly associated with length of stay.

Result

Out of 512 enrolled participants, 495 were participated with a response rate of 96.7%. The prevalence of prolonged length of stay in the adult emergency department was 46.5% (95%CI: 42.1, 51.1). Lack of insurance (AOR: 2.11; 95% CI: 1.22, 3.65), non-communicative presentation (AOR: 1.98; 95% CI: 1.07, 3.68), delayed consultation (AOR: 9.5; 95% CI: 5.00, 18.03), overcrowding (AOR: 4.98; 95% CI: 2.13, 11.68), and shift change experience (AOR: 3.67; 95% CI: 1.30, 10.37) were significantly associated with prolonged length of stay.

Conclusion

The result of this study is found to be high based on Ethiopian target emergency department patient length of stay. Lack of insurance, presentation without communication, delayed consultation, overcrowding, and shift change experience were significant factors for prolonged emergency department length of stay. Therefore, interventions like expansion of organizational setup are needed to decrease the length of stay to an acceptable level.
Recruitment to a trial of antipsychotic reduction: impact of an acceptability study
Authors: Ramsay Georgina , Haime Zoë , Crellin Nadia E , Stansfeld Jacki L , Priebe Stefan , Long Maria , Moncrieff Joanna
Published: March 2023

Objectives

Pre-trial acceptability studies may boost recruitment, especially in trials comparing distinctly different interventions. We evaluated the impact of an acceptability study on recruitment to a randomised trial of antipsychotic reduction versus maintenance treatment and explored demographic and clinical predictors of subsequent enrolment.

Methods

Participants with a diagnosis of a schizophrenia spectrum disorder who were taking antipsychotic medication were interviewed about their views of taking part in a future trial.

Results

In a sample of 210 participants, 151 (71.9%) expressed an interest in taking part in the future trial, 16 (7.6%) said they might be interested, and 43 (20.5%) said they were not. Altruistic reasons were most commonly given for wanting to take part, and concern about randomisation for not wanting to. Ultimately 57 people enrolled in the trial (27.1% of the original sample). Eighty-five people who initially expressed an interest did not enrol due to declining or not being eligible (for clinical reasons). Women and people from a white ethnic background were more likely to enrol in the trial, but no illness or treatment-related characteristics were associated with enrolment.

Conclusion

An acceptability study can be a useful tool for recruitment to challenging trials, but it may over-estimate recruitment.
External validation of the American prediction model for incident type 2 diabetes in the Iranian population
Authors: Asgari Samaneh , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad
Published: March 2023

Background

The primary aim of the present study was to validate the REasons for Geographic and Racial Differences in Stroke (REGARDS) model for incident Type 2 diabetes (T2DM) in Iran.

Methods

Present study was a prospective cohort study on 1835 population aged ≥ 45 years from Tehran lipids and glucose study (TLGS).The predictors of REGARDS model based on Bayesian hierarchical techniques included age, sex, race, body mass index, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose. For external validation, the area under the curve (AUC), sensitivity, specificity, Youden’s index, and positive and negative predictive values (PPV and NPV) were assessed.

Results

During the 10-year follow-up 15.3% experienced T2DM. The model showed acceptable discrimination (AUC (95%CI): 0.79 (0.76–0.82)), and good calibration. Based on the highest Youden’s index the suggested cut-point for the REGARDS probability would be ≥ 13% which yielded a sensitivity of 77.2%, specificity 66.8%, NPV 94.2%, and PPV 29.6%.

Conclusions

Our findings do support that the REGARDS model is a valid tool for incident T2DM in the Iranian population. Moreover, the probability value higher than the 13% cut-off point is stated to be significant for identifying those with incident T2DM.
Effect of including a dietary supplement of raisins, a food rich in polyphenols, on cognitive function in healthy older adults; a study protocol for a randomized clinical trial
Authors: Rodrigo-Gonzalo María J. , Recio-Rodríguez José I. , Méndez-Sánchez Roberto , Pablos-Hernández María C. , González-Ramírez Alfonso , González-Sánchez Jesús , Fermoso-Palmero María J. , Puente-González Ana S. , Sánchez-Sánchez María C. , Barbero-Iglesias Fausto J. , Rihuete-Galve María I. , González-Manzano Susana
Published: March 2023

Background

Polyphenols have been shown to be effective against many chronic diseases, including neurodegenerative diseases. Specifically, the consumption of raisins, being a food rich in polyphenols, has been attributed with neuroprotective benefits. Therefore, our main objective is to evaluate the effect of including 50 g of raisins in the diet daily for 6 months, on the improvement of cognitive performance, cardiovascular risk factors and markers of inflammation in a population of older adults without cognitive impairment.

Methods

Design and intervention: This study will be a randomized controlled clinical trial of two parallel groups. Each subject included in the study will be randomly assigned to one of two study groups: control group (no supplement), intervention group (50 g of raisins daily during 6 months).

Study population: The participants will be selected by consecutive sampling in the Primary Care consultations of urban health centers in Salamanca and Zamora (Spain), taking into account the selection criteria.

Study variables: Two visits will be made, baseline and at 6 months. Cognitive performance will be evaluated (Mini-Mental State Examination test, Rey Auditory Verbal Learning Test, verbal fluency and montreal cognitive assessment (Moca)). It will also be analyzed the level of physical activity, quality of life, activities of daily living, energy and nutritional composition of the diet, body composition, blood pressure, heart rate, markers of inflammation and other laboratory tests of clinical relevance (glycaemia, total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides). In addition, sociodemographic data, personal and family history, medication use and alcohol and tobacco consumption will be collected.

Discussion

In this project, it is intended to contribute to minimize the problems derived from cognitive deterioration in older people.

Trial registration

ClincalTrials.gov Identifier: NCT04966455 Registration date: July 1, 2021.
The distribution characteristics of global blaOXA-carrying Klebsiella pneumoniae
Authors: Meng Lingning , Liu Ziyao , Liu Chang , Li Chuchu , Shen Han , Cao Xiaoli
Published: March 2023

Objective

To analyze the distribution of blaOXA among global Klebsiella pneumoniae and the characteristics of blaOXA-carrying K. pneumoniae.

Materials and Methods

The genomes of global K. pneumoniae were downloaded from NCBI by Aspera software. After quality check, the distribution of blaOXA among the qualified genomes was investigated by annotation with the resistant determinant database. The phylogenetic tree was constructed for the blaOXA variants based on the single nucleotide polymorphism (SNP) to explore the evolutionary relationship between these variants. The MLST (multi-locus sequence type) website and blastn tools were utilized to determine the sequence types (STs) of these blaOXA-carrying strains. and sample resource, isolation country, date and host were extracted by perl program for analyzing the characteristics of these strains.

Results

A total of 12,356 K. pneumoniae genomes were downloaded and 11,429 ones were qualified. Among them, 4386 strains were found to carry 5610 blaOXA variants which belonged to 27 varieties of blaOXAs, blaOXA-1 (n = 2891, 51.5%) and blaOXA-9 (n = 969, 17.3%) were the most prevalent blaOXA variants, followed by blaOXA-48 (n = 800, 14.3%) and blaOXA-232 (n = 480, 8.6%). The phylogenetic tree displayed 8 clades, three of them were composed of carbapenem-hydrolyzing oxacillinase (CHO). Totally, 300 distinct STs were identified among 4386 strains with ST11 (n = 477, 10.9%) being the most predominant one followed by ST258 (n = 410, 9.4%). Homo sapiens (2696/4386, 61.5%) was the main host for blaOXA-carrying K. pneumoniae isolates. The blaOXA-9-carrying K. pneumoniae strains were mostly found in the United States and blaOXA-48-carrying K. pneumoniae strains were mainly distributed in Europe and Asia.

Conclusion

Among the global K. pneumoniae, numerous blaOXA variants were identified with blaOXA-1, blaOXA-9, blaOXA-48 and blaOXA-232 being the most prevalent ones, indicating that blaOXA rapidly evolved under the selective pressure of antimicrobial agents. ST11 and ST258 were the main clones for blaOXA-carrying K. pneumoniae.
Intraoperative hemodialysis during open-heart surgery in patients with severe chronic kidney disease: a retrospective cohort study
Authors: Inoue Takahiro , Kuji Hiroshi , Nagaoka Kanako , Akanuma Takafumi , Fukuda Junko , Matsui Hiroki , Tanabe Hiroaki , Ohara Mamiko , Suzuki Tomo
Published: March 2023

Background

Acute kidney injury and chronic kidney disease (CKD) after cardiac surgery are associated with poor renal prognosis and increased mortality. The impact of intraoperative hemodialysis (IHD) on postoperative renal function remains unknown. We aimed to evaluate the utility of IHD during open-heart surgery in patients with severe non-dialysis-dependent chronic kidney disease (CKD-NDD) and its association with clinical outcomes.

Methods

This was a single-center retrospective cohort study that employed IHD during non-emergency open-heart surgery in patients with CKD stage G4 or G5. Patients who underwent emergent surgery, chronic dialysis, and/or kidney transplantation were excluded. We retrospectively compared the clinical characteristics and outcomes between patients from the IHD and non-IHD groups. The primary outcomes were 90-day mortality and postoperative initiation of renal replacement therapy (RRT).

Results

Twenty-eight patients were categorized into the IHD group and 33 into the non-IHD group. When comparing the IHD and non-IHD groups, men accounted for 60.7 vs. 50.3% of patients, the mean patient age was 74.5 (standard deviation [SD] 7.0) vs. 72.9 (SD 9.4) years (p = 0.744), and the proportion of patients with CKD G4 was 67.9 vs. 84.9% (p = 0.138). Regarding clinical outcomes, no significant differences were observed in the 90-day mortality (7.1 vs. 3.0%; p = 0.482) and 30-day RRT (17.9 vs. 30.3%; p = 0.373) rates between the groups. Among the patients with CKD G4, the IHD group had significantly lower 30-day RRT rates than the non-IHD group (0 vs. 25.0%; p = 0.032). RRT initiation was less likely for patients with CKD G4 (odds ratio 0.07, 95% confidence interval [CI] 0.01–0.37; p = 0.002); however, IHD did not significantly decrease the incidence of poor clinical outcomes (odds ratio 0.20, 95% CI 0.04–1.07; p = 0.061).

Conclusions

IHD during open-heart surgery in patients with CKD-NDD did not improve their clinical outcomes with regards to postoperative dialysis. However, for patients with CKD G4, IHD may be useful for postoperative cardiac management.
Palatal myoclonus and hypertrophic olivary degeneration following wernekinck commissure syndrome: a case report
Authors: Zhang Qian , Guo Jiahuan , Zhao Xingquan , Zhang Xinghu , Ma Yuetao
Published: March 2023

Background

Hypertrophic olivary degeneration (HOD), a rare form of transsynaptic degeneration, is secondary to dentato-rubro-olivary pathway injuries in some cases. We describe a unique case of an HOD patient who presented with palatal myoclonus secondary to Wernekinck commissure syndrome caused by a rare bilateral “heart-shaped” infarct lesion in the midbrain.

Case presentation

A 49-year-old man presented with progressive gait instability in the past 7 months. The patient had a history of posterior circulation ischemic stroke presenting with diplopia, slurred speech, and difficulty in swallowing and walking 3 years prior to admission. The symptoms improved after treatment. The feeling of imbalance appeared and was aggravated gradually in the past 7 months. Neurological examination demonstrated dysarthria, horizontal nystagmus, bilateral cerebellar ataxia, and 2–3 Hz rhythmic contractions of the soft palate and upper larynx. Magnetic resonance imaging (MRI) of the brain performed 3 years prior to this admission showed an acute midline lesion in the midbrain exhibiting a remarkable “heart appearance” on diffusion weighted imaging. MRI after this admission revealed T2 and FLAIR hyperintensity with hypertrophy of the bilateral inferior olivary nucleus. We considered a diagnosis of HOD resulting from a midbrain heart-shaped infarction, which caused Wernekinck commissure syndrome 3 years prior to admission and later HOD. Adamantanamine and B vitamins were administered for neurotrophic treatment. Rehabilitation training was also performed. One year later, the symptoms of this patient were neither improved nor aggravated.

Conclusion

This case report suggests that patients with a history of midbrain injury, especially Wernekinck commissure injury, should be alert to the possibility of delayed bilateral HOD when new symptoms occur or original symptoms are aggravated.
Resting-state functional connectivity in multiple sclerosis patients receiving nabiximols for spasticity
Authors: Gajofatto Alberto , Cardobi Nicolò , Gobbin Francesca , Calabrese Massimiliano , Turatti Marco , Benedetti Maria Donata
Published: March 2023

Background

Nabiximols (Sativex®) is a cannabinoid approved for multiple sclerosis (MS)-related spasticity. Its mechanism of action is partially understood, and efficacy is variable.

Objective

To conduct an exploratory analysis of brain networks connectivity changes on resting state (RS) functional MRI (fMRI) of MS patients treated with nabiximols.

Methods

We identified a group of MS patients treated with Sativex® at Verona University Hospital, who underwent RS brain fMRI in the 4 weeks before (T0) and 4–8 weeks after (T1) treatment start. Sativex® response was defined as ≥ 20% spasticity Numerical Rating Scale score reduction at T1 vs. T0. Connectivity changes on fMRI were compared between T0 and T1 in the whole group and according to response status. ROI-to-ROI and seed-to-voxel connectivity were evaluated.

Results

Twelve MS patients (7 males) were eligible for the study. Seven patients (58.3%) resulted Sativex® responders at T1. On fMRI analysis, Sativex® exposure was associated with global brain connectivity increase (particularly in responders), decreased connectivity of motor areas, and bidirectional connectivity changes of the left cerebellum with a number of cortical areas.

Conclusions

Nabiximols administration is associated with brain connectivity increase of MS patients with spasticity. Modulation of sensorimotor cortical areas and cerebellum connectivity could play a role in nabiximols effect.
Menstrual, fertility and psychological impacts after uterine compression sutures for postpartum hemorrhage: a prospective cohort study
Authors: Kwong Lee Ting , Wong Sai Fun , So Po Lam
Published: March 2023

Background

Uterine compression suture is an important conservative surgical technique in managing atonic postpartum hemorrhage. In this study, we aim to evaluate the subsequent menstrual, fertility and psychological outcomes after uterine compression sutures.

Methods

This was a prospective cohort study between 2009 and 2022 conducted in a tertiary obstetric unit (6000 deliveries per year) in Hong Kong SAR. Women with primary postpartum hemorrhage successfully treated with uterine compression sutures were followed-up in postnatal clinic for two years after delivery. Data on menstrual pattern were collected during each visit. Psychological impact after uterine compression suture was assessed using a standardized questionnaire. Subsequent pregnancies were identified by territory-wide computer registry and telephone interviews. Women with postpartum hemorrhage treated with uterotonic agents only were chosen as controls.

Results

In our cohort (n = 80), 87.9% of women had return of menses within six months after delivery. Regular monthly cycle was observed in 95.6% of women. Majority of women reported similar menstrual flow (75%), menstrual days (85.3%) and no change in dysmenorrhea status (88.2%) as compared before. Among eight (11.8%) women who reported hypomenorrhea after uterine compression sutures, two cases of Asherman’s syndrome were diagnosed. Among 23 subsequent pregnancies (16 livebirths), no significant differences in outcome were observed except more omental or bowel adhesions (37.5% vs. 8.8%, p = 0.007), recurrence of hemorrhage (68.8% vs. 7.5%, p < 0.001) and repeated compression sutures (12.5% vs. 0%, p = 0.024) were seen in women with previous compression sutures. Over half of the couple declined future fertility after uterine compression sutures with 38.2% of women recalled unpleasant memories and 22.1% reported life-long adverse impact especially tokophobia.

Conclusion

Majority of women with history of uterine compression sutures had similar menstruation and pregnancy outcomes as compared to those who did not have sutures. However, they had higher intrapartum risk of visceral adhesions, recurrence of hemorrhage and repeated compression sutures next pregnancy. Furthermore, couple could be more susceptible to negative emotional impact.
Predictive value of 3D ultrasound assessment of endometrial receptivity for PGD/PGS for transfer pregnancy outcome
Authors: Sun Kaixuan , Xiu Yinling , Wang Yinghua , Yu Tingting , Lu Xiaoli , Wang Xiliang , Yu Yuexin
Published: March 2023

Objective

To investigate the predictive value of three-dimensional ultrasound assessment of endometrial receptivity in PGD/PGS transplantation patients on pregnancy outcome.

Methods

280 patients undergoing PGD/PGS transplantation were enrolled and divided into group A and group B according to the patients’ pregnancy outcomes. The general conditions, endometrial receptivity indexes of the two groups were compared. Multifactorial logistic regression analysis was used to determine the factors influencing pregnancy outcome in PGD/PGS transplant patients. ROC curves were plotted to analyze the predictive value of 3D ultrasound parameters on pregnancy outcome. The results of the study were validated with patients who underwent FET transplantation, and the patients in the validation group were treated with the same 3D ultrasound examination method and treatment plan as the observation group.

Results

The differences in basic situations between two groups were not statistically significant (P > 0.05). The percentage of endometrial thickness, endometrial blood flow, and endometrial blood flow classification type II + II were higher in group A than in group B (P < 0.05). Multifactorial logistic regression analysis showed that endometrial thickness, endometrial blood flow and endometrial blood flow classification were influencing factors of pregnancy outcome in PGD/PGS patients. The sensitivity of predicting pregnancy outcome based on the results of transcatheter 3D ultrasound was 91.18%, the specificity was 82.35%, and the accuracy was 90.00%, which has a high predictive value.

Conclusion

3D ultrasound can predict pregnancy outcome by assessing the endometrial receptivity of PGD/PGS transplantation, in which endometrial thickness and endometrial blood flow have a good predictive value.
Role of cortical excitatory/inhibitory imbalance in autism spectrum disorders from a symptom severity trajectories framework: a study protocol
Authors: Colomar Laura , San José Cáceres Antonia , Álvarez-Linera Juan , González-Peñas Javier , Huertas Patón Abigail , Martín de Blas Daniel , Polo Arrondo Ana Paloma , Solís Andrea , Jones Emily , Parellada Mara
Published: March 2023

Background

There is considerable evidence reporting an excitatory/inhibitory (E/I) cortical imbalance in autism spectrum disorders (ASD). However, previous findings on the direction of this imbalance and its relationship to ASD symptomatology are heterogeneous. Some factors contributing to these mixed results might be the methodological differences between studies assessing the E/I ratio and the intrinsic variability within the autistic spectrum. Studying the evolution of ASD symptoms and the factors that modulate it might help to explain and reduce this variability. Here we present a study protocol to explore the longitudinal role of E/I imbalance in ASD symptoms, combining different approaches to measure the E/I ratio and using the trajectories of symptom severity as a framework.

Methods

This observational two time-point prospective study assesses the E/I ratio and the evolution of the behavioural symptoms in a sample of at least 98 participants with ASD. Participants are enrolled at 12 to 72 months of age and followed from 18 to 48 months after. A comprehensive battery of tests is applied to evaluate ASD clinical symptoms. The E/I ratio is approached from electrophysiology, magnetic resonance, and genetics. We will calculate the individual change for the main ASD symptoms and, based on that, we will define the trajectories of symptom severity. Then, we will investigate the correlation between measures of excitation/inhibition balance and autistic symptomatology cross-sectionally, as well as the ability of these measurements to predict changes in symptoms over time.

Discussion

This study presents a robust multisystemic approach to the E/I imbalance theory in autism and its relation to divergent symptom trajectories. That setting will allow us to relate and compare the neurobiological information coming from different sources and its impact on behavioural symptoms while accounting for the high variability in ASD. The findings derived from this study could contribute to the ASD biomarkers research and might provide valuable evidence for the development of more personalized treatments in ASD.
Comparison of the prognostic value of a comprehensive set of predictors in identifying risk of metabolic-associated fatty liver disease among employed adults
Authors: Yang Ze , Yu Bin , Wang Zihang , Li Zhitao , Yang Bo , Zeng Honglian , Yang Shujuan
Published: March 2023

Objective

Metabolic-associated fatty liver disease (MAFLD) is of concern in employed adults, while the crucial indicators in predicting MAFLD are understudied in this population. We aimed to investigate and compare the prediction performance of a set of indicators for MAFLD in employed adults.

Methods

A cross-sectional study recruiting 7968 employed adults was conducted in southwest China. MAFLD was assessed by abdominal ultrasonography and physical examination. Comprehensive indicators of demographics, anthropometric, lifestyle, psychological, and biochemical indicators were collected by questionnaire or physical examination. All indicators were evaluated for importance in predicting MAFLD by random forest. A prognostic model based on multivariate regression model was constructed to obtain a prognostic index. All indicators and prognostic index were compared to evaluate their prediction performance in predicting MAFLD by the receiver operating characteristic (ROC) curve, calibration plot, and Decision curve analysis (DCA).

Results

Triglyceride Glucose-Body Mass Index (TyG-BMI), BMI, TyG, triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C), and TG ranked the top five important indicators, and TyG-BMI performed the most accurate prediction of MAFLD according to the ROC curve, calibration plot and DCA. The area under the ROC curves (AUCs) of the five indicators were all over 0.7, with TyG-BMI (cut-off value: 218.284, sensitivity: 81.7%, specificity: 78.3%) suggesting the most sensitive and specific indicator. All five indicators showed higher prediction performance and net benefit than the prognostic model.

Conclusion

This epidemiological study firstly compared a set of indicators to evaluate their prediction performance in predicting MAFLD risk among employed adults. Intervention targeting powerful predictors can be helpful to reduce the MAFLD risk among employed adults.
Women’s empowerment and nutritional status of children in the Gambia: further analysis of the 2020 Gambia demographic and health survey
Authors: Sey-Sawo Jainaba , Sarr Francis , Bah Haddy Tunkara , Senghore Thomas
Published: March 2023

Empowering women and the promotion of children’s health are key components of the Sustainable Development Goals targeted for achievement by 2030. The survival of young children, which depends on their nutrition, is influenced by an interaction of factors at the household level. This study aims to investigate the association between women’s empowerment and undernutrition among children under age 5 using The Gambia Demographic Health Survey (GDHS) 2019–20.

Children’s undernutrition was measured with two indicators: stunting and underweight. The women’s empowerment indicators were educational status, employment, decision making, age at first sex and age at first birth, and acceptance of wife beating. StataSE software Version 17 was used for data analysis. Analyses were cluster-adjusted, sample-weighted, with confounding/moderating variables. Descriptive statistics and cross-tabulations were computed for all variables. Bivariate and multivariate analysis of the outcomes and women’s empowerment were conducted.

The prevalence of stunting and underweight among the children under age 5 was 17% and 12%, respectively. The results of the multiple logistic regression show that women with no education had 51% (OR = 1.51; 95% CI = 1.11–2.07; p = 0.009), and 52% (OR = 1.52; 95% CI = 1.06–2.14; p = 0.022) greater odds of having children under age 5 who were stunted or underweight compared to those women with primary and higher level of education, respectively. Mothers with a body mass index classified as thin were associated with an increased odds of having stunted (OR = 1.44; 95% CI 1.01–2.05; p = 0.033) and underweight (OR = 1.69; 95% CI = 1.58–3.52; P < 0.001) children. In addition, women who reported accepting wife beating had 69% (OR = 1.69; 95% CI 1.22–2.35; p = 0.002) and 66% (OR = 1.66; 95% CI 1.15–2.40; p = 0.006) greater odds of having stunted and underweight children respectively compared to those who did not accept wife beating.

In conclusion, the result of this study shows that women’s empowerment is associated with undernutrition among children under age 5 in The Gambia. This is suggesting that implementing policies and interventions that increase the empowerment of women will contribute to the improvement of child nutrition in the country.
Binary classification of users of electronic cigarettes and smokeless tobacco through biomarkers to assess similarity with current and former smokers: machine learning applied to the population assessment of tobacco and health study
Authors: Ohara Hiromi , Ito Shigeaki , Takanami Yuichiro
Published: March 2023

Background

Exposure to harmful and potentially harmful constituents in cigarette smoke is a risk factor for cardiovascular and respiratory diseases. Tobacco products that could reduce exposure to these constituents have been developed. However, the long-term effects of their use on health remain unclear. The Population Assessment of Tobacco and Health (PATH) study is a population-based study examining the health effects of smoking and cigarette smoking habits in the U.S. population. Participants include users of tobacco products, including electronic cigarettes and smokeless tobacco. In this study, we attempted to evaluate the population-wide effects of these products, using machine learning techniques and data from the PATH study.

Methods

Biomarkers of exposure (BoE) and potential harm (BoPH) in cigarette smokers and former smokers in wave 1 of PATH were used to create binary classification machine-learning models that classified participants as either current (BoE: N = 102, BoPH: N = 428) or former smokers (BoE: N = 102, BoPH: N = 428). Data on the BoE and BoPH of users of electronic cigarettes (BoE: N = 210, BoPH: N = 258) and smokeless tobacco (BoE: N = 206, BoPH: N = 242) were input into the models to investigate whether these product users were classified as current or former smokers. The disease status of individuals classified as either current or former smokers was investigated.

Results

The classification models for BoE and BoPH both had high model accuracy. More than 60% of participants who used either one of electronic cigarettes or smokeless tobacco were classified as former smokers in the classification model for BoE. Fewer than 15% of current smokers and dual users were classified as former smokers. A similar trend was found in the classification model for BoPH. Compared with those classified as former smokers, a higher percentage of those classified as current smokers had cardiovascular disease (9.9–10.9% vs. 6.3–6.4%) and respiratory diseases (19.4–22.2% vs. 14.2–16.7%).

Conclusions

Users of electronic cigarettes or smokeless tobacco are likely to be similar to former smokers in their biomarkers of exposure and potential harm. This suggests that using these products helps to reduce exposure to the harmful constituents of cigarettes, and they are potentially less harmful than conventional cigarettes.
Precision shaping of elastic stable intramedullary nail for the treatment of metaphyseal diaphysis junction fracture of the distal radius in children: a preliminary report in two centers
Authors: Chaoyu Liu , Guoqiang Jia , Wenqiang Xu , Lian Meng , Jing Shan , Yong Liu
Published: March 2023

Background

This study introduces a novel retrograde precision shaping elastic stable intramedullary nailing (ESIN-RPS) technique and reports clinical outcomes in pediatric distal radius metaphyseal diaphysis junction (DRMDJ) fracture.

Methods

Data about DRMDJs were collected from February 1, 2020, to April 31, 2022 at two hospitals, retrospectively. All patients were treated with closed reduction and ESIN-RPS fixation. The operation time, blood loss, fluoroscopy times, alignment, and residual angulation on X-ray were recorded. At the last follow-up, the function of wrist and forearm rotation were evaluated.

Results

Totally, 23 patients were recruited. The mean time of follow-up was 11 months and the minimum was 6 months. The mean operation time was 52 min, and the mean fluoroscopies pulses were 6 times. The postoperative anterioposterior (AP) alignment was 93 ± 4% and the lateral alignment was 95 ± 3%. The postoperative AP angulation was (4 ± 1)°, and the lateral angulation was (3 ± 1)°. At the last follow-up, the evaluation of the Gartland and Werley demerit criteria of wrist revealed 22 excellent cases and 1 good case. The forearm rotation and thumb dorsiflexion functions were not limited.

Conclusion

The ESIN-RPS is a novel, safe, and effective method for the treatment of pediatric DRMDJ fracture.
Treatment strategies for recurrent dislocation following total hip arthroplasty: relationship between cause of dislocation and type of revision surgery
Authors: Toyoda Takashi , Oe Kenichi , Iida Hirokazu , Nakamura Tomohisa , Okamoto Naofumi , Saito Takanori
Published: March 2023

Background

There are many therapeutic options for dislocation following total hip arthroplasty (THA). The aim of this study was to evaluate the results of revision surgery for dislocated hips.

Methods

Between November 2001 and December 2020, 71 consecutive revision hip surgeries were performed at our institution for recurrent dislocation following THA. We conducted a retrospective study of all 65 patients (71 hips), who were followed for a mean of 4.7 ± 3.2 years (range, 1–14). The cohort included 48 women and 17 men, with a mean age of 71 ± 12.3 years (range, 34–92). The mean number of previous surgeries was 1.6 ± 1.1 (range, 1–5). From intraoperative findings, we created six categories of revision hip surgery for recurrent dislocation following THA: open reduction and internal fixation (2 hips); head change or liner change only (6 hips); cup change with increased head size only (14 hips); stem change only (7 hips); cup and stem change (24 hips); and conversion to constrained cup (18 hips). Prosthesis survival was analyzed by the Kaplan-Meier method, with repeat revision surgery for re-dislocation or implant failure as the endpoint. A cox proportional hazards model was used for risk factors of re-revision surgery.

Results

Re-dislocation occurred in 5 hips (7.0%) and implant failure in 1 hip (1.4%). The 10-year survival rate was 81.1% (95% confidence interval, 65.5–96.8). A Dorr classification of “positional” was a risk factor for re-revision surgery due to re-dislocation.

Conclusion

Clear understanding of the cause of dislocation is essential for optimizing revision procedures and improving the rate of successful outcomes.
Preliminary study on the predictive value of the vasoactive-inotropic score for the prognosis of neonatal congenital diaphragmatic hernia
Authors: Liu Chao , Li Jingna , Wei Yandong , Wang Ying , Zhang Hui , Ma Lishuang
Published: March 2023

Background

No study has reported on the relationship between the vasoactive-inotropic score (VIS) and the prognosis of neonates with a severe congenital diaphragmatic hernia (CDH). This study aimed to identify potential risk factors for mortality in patients with CDH. We calculated the VIS based on the vasoactive drugs used during the perioperative period to investigate the relationship between VIS and infant prognosis.

Methods

We retrospectively analyzed the clinical data of 75 neonates with CDH who were treated at our center between January 2016 and October 2021. We calculated the maximum and mean VIS during the first 24 h of hospitalization (hosVIS [24max] and hosVIS [24mean], respectively) and after surgery (postVIS [24max] and postVIS [24mean], respectively). The relationship between the VIS and the prognosis of neonates with CDH was analyzed using a receiver operating characteristic (ROC) curve, t-test, chi-square test, rank-sum test, and logistic regression analysis.

Results

In total, 75 participants with CDH were included in the study. The chance of survival was 80%. Our results showed that hosVIS (24max) was an accurate predictor of prognosis (area under the ROC curve = 0.925, p = 0.007). The calculated optimal critical value of hosVIS (24max) for predicting a poor prognosis was 17 (J = 0.75). Multivariate analysis revealed that hosVIS (24max) was an independent risk factor for death in neonates with CDH.

Conclusion

In neonates with CDH, a higher VIS, especially hosVIS (24max), suggests worsened cardiac function, a more severe condition, and a higher risk of death. The rising VIS score in infants prompts physicians to implement more aggressive treatment to improve cardiovascular function.