bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis
Authors: Qin Min , Chao Lingxi , Liu Shiqun
Published: January 2025

Background:

This study evaluates the efficacy and safety of sitagliptin versus gliclazide, combined with metformin, in treatment-naive patients with type 2 diabetes mellitus (T2DM) and glucotoxicity.

Methods:

In this single-center, randomized, controlled noninferiority trial, 129 treatment-naive patients with T2DM with glucotoxicity (fasting plasma glucose [FPG] ≥ 200 mg/dL and glycated hemoglobin ≥ 9.0%) were randomized to receive sitagliptin plus metformin (n = 66) or gliclazide plus metformin (n = 63) for 12 weeks. Sitagliptin and gliclazide were given for the first 4 weeks, followed by metformin monotherapy for 8 weeks. Efficacy end points included changes in glycemic control, body weight, and β-cell function at baseline, 4 weeks, and 12 weeks.

Results:

After 12 weeks, mean glycated hemoglobin reductions were 4.03% in the sitagliptin group and 4.13% in the gliclazide group, with a mean difference of −0.097 (95% confidence interval, −0.648 to 0.453), confirming noninferiority. Both groups showed significant FPG reductions at 4 weeks (P < .05). The sitagliptin group achieved faster glycemic targets, greater FPG and body weight reductions, and higher rates of FPG < 6.1 mmol/L (26.2% vs 5.7%; P = .012). No significant differences were observed in β-cell function or hypoglycemia incidence (P > .05). Genetic analysis showed specific single-nucleotide polymorphisms affected drug efficacy: dipeptidyl peptidase-4 rs2909451 TT and rs4664443 GG genotypes showed lower efficacy with sitagliptin, while GLP1R rs3765467 AG and KCNJ11 rs2285676 CC genotypes responded better to sitagliptin.

Conclusion:

Sitagliptin combined with metformin is noninferior to gliclazide combined with metformin in treatment-naive patients with T2DM with glucotoxicity. Genetic polymorphisms significantly affect drug efficacy, highlighting the importance of personalized medicine. The sitagliptin group achieved glycemic targets more quickly and had greater weight reductions without increased adverse effects.
Age-related changes in bioelectrical impedance analysis-derived phase angle (PhA) and the association between PhA and sarcopenic obesity in Chinese adults
Authors: Luo Xi , Jin Weiwei
Published: January 2025

There are limited studies on the phase angle (PhA) and sarcopenic obesity (SO) in the Chinese population. This study aimed to establish 50 kHz-PhA reference data for SO population, and to evaluate the correlation between 50 kHz-PhA and SO. A total of 10,312 participants including 5415 men and 4897 women were enrolled in this study, and their resistance and reactance at 50 kHz, and body composition parameters were measured a segmental multifrequency bioelectrical impedance analysis device (InBody 720). Participants were compared between the SO and non-SO groups. Then, age and fat parameters related changes in PhA were evaluated. Furthermore, Receiver Operating Characteristic (ROC) curves were used to identify the optimal PhA cutoff values for detecting SO in males and females. The results showed significant differences in PhA and body composition parameters between the SO group and the non-SO group in both sexes (P < .001), and the prevalence rates of SO increase with age in both sexes (P < .001). The PhA values decrease with age, with a significant decrease beginning at age 65 years for males and 66 years for females. The accumulation of excess adipose tissue was also found to be associated with decrease in 50 kHz-PhA value. Furthermore, PhA was negatively associated with SO, independent of age and sex. The area under the ROC curve (AUC) of PhA for SO was 0.790 (95% CI: 0.746–0.833, P < .001) in males and 0.763 (95% CI: 0.702–0.825, P < .001) in females. The optimal cutoff value was ≤ 5.55° (specificity 0.693, sensitivity 0.759) for males and ≤4.79° (specificity 0.687, sensitivity 0.738) for females. In conclusion, 50 kHz-PhA can be used as a predictor of SO, with cutoff values of ≤5.55° for males and ≤4.79° for females. This simple and practical method of using 50 kHz-PhA to predict SO could be valuable in clinical practice.
Comparative study on blood pressure and metabolic improvements in hypertensive patients using copper bianstone scraping
Authors: Qian Ying , Yuan Lan , Zhang Xing
Published: January 2025

To evaluate the effectiveness and feasibility of the copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy program by comparing and analyzing the improvement of blood pressure, blood lipids and blood glucose in hypertensive patients who received copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy intervention. We selected 160 cases of hypertensive patients from July 2022 to March 2024 for the study. They were divided into 80 cases in the comparison group and 80 cases in the observation group according to whether or not they underwent copper bianstone scraping combined with Chinese modified dietary therapy for termination of hypertension. In the comparison group, conventional Chinese dietary therapy with improved termination of hypertension was used, and in the observation group, copper bianstone scraping combined with Chinese dietary therapy with improved termination of hypertension (DASH) was used on the basis of the comparison group. Differences in vitamin D, Homocysteine and serum calcium levels, blood pressure, blood glucose and lipid levels were compared between the 2 groups. The decreases of glycosylated hemoglobin, fasting blood glucose and 2-hour postprandial blood glucose in the observation group were greater than those in the comparison group; the decreases of blood pressure and BMI in the observation group were greater than those in the comparison group. The difference in comparison was statistically significant (P-value < 0.05). After the intervention, the improvement of homocysteine, vitamin D, serum calcium, albumin, hemoglobin and transferrin in the observation group was greater than that in the comparison group, and the difference was statistically significant (P-value < 0.05). Copper bianstone scraping combined with Chinese modified termination of hypertension dietary therapy in hypertensive patients has a better effect, can effectively improve the patient’s blood glucose and lipid levels, improve the nutritional status of the patient, can be promoted in the rehabilitation management of hypertension.
Effects of intensive wearing face masks on patients with postinfectious cough: A randomized controlled trial
Authors: Lan Shan , Pan Lun , Qin Yang , Ma Lijie , Yi Hongyu
Published: January 2025

Background:

Postinfectious cough was a common clinical symptom, which troubled patients and increased economic burden. The efficacy of pharmacotherapy for this symptom was unsatisfactory. This study aimed to explore the intervention effect of intensified mask-wearing on patients with post-upper respiratory tract infection cough and its role in reducing the economic burden of patients.

Methods:

As a randomized, controlled, single-blind trial, a total of 46 eligible patients with postinfectious cough were selected from local hospital, from November 2023 to February 2024. They were randomized into a control group (n = 21) and an experimental group (n = 25). Both groups received routine diagnosis and treatment, and the experimental group additionally received wearing medical surgical masks for >8 hours every day. All patients were followed up by on-site evaluation or telephone follow-up every 3 days for 3 weeks. We used a cough evaluation test to evaluate symptoms, recorded mask-wearing duration, and adjusted the treatment plan.

Results:

There were no statistically significant differences in age, gender, course of disease, cough severity, and time of wearing face masks in the early stage between 2 groups (P > .05). Three people (12.0%) in the experimental group were excluded from the study because of substandard wearing face masks. The average daily mask-wearing time of the experimental and control groups were: 9.7 ± 0.9 versus 1.2 ± 2.2 hours (P < .001). There was a statistically significant difference in cough severity scores between 2 groups on the 9th day of follow-up, 6.6 ± 2.0 versus 8.0 ± 2.5 (P < .05), the markedly effective and total effective rates were: 86.4% versus 57.1% and 31.81% versus 38.09 % (P <.05). The treatment time for all patients in 2 groups to achieve effectiveness was: 10.1 ± 4.6 versus 13.0 ± 4.1 days (P < .05). The final medical expenditure of 2 groups were 289.4 (185.2, 782.2) CNY versus 717.5 (548.5, 1582.2) CNY (P < .05).

Conclusion:

The compliance of patients with intensive wearing face masks was high. The intensive wearing of face masks had a good intervention effect on the treatment of postinfectious cough, which could effectively reduce cough symptoms of patients, shorten the course of the disease, and reduce medical expenditure.
Correlation of red blood cell parameters and platelet count among adult anemic patients attending Madda Walabu University Goba Referral Hospital, Goba, Southeast Ethiopia: A comparative cross-sectional study
Authors: Jundi Mohammedamin , Tadasa Edosa , Adissu Wondimagegn
Published: January 2025

Anemia is a worldwide public health problem and is associated with platelet disorders. The relationship between anemia and platelets is complex, with the association being either normal platelet count or thrombocytosis. Platelets are significantly decreased in patients with anemia, and thrombocytopenia has been documented in patients with severe anemia. There are few reports in the literature on the correlation between platelet count and red blood cell parameters in anemic patients. Therefore, this study aimed to compare the correlation between red blood cell parameters and platelet count in adult anemic patients attending Madda Walabu University Goba Referral Hospital (MWUGRH): Goba, Southeast Ethiopia, from May 30 to July 30, 2022. A cross-sectional comparative study was conducted among 352 subjects (176 anemic and 176 controls) who attended the hospital during the study period and were recruited using a convenient sampling technique. Sociodemographic and other relevant variables were collected using a structured questionnaire. Four milliliters of venous blood were collected and placed in a K2EDTA tube for analysis of hematologic parameters using the Sysmex XN-550 (Sysmex Corp., Japan) automated hematology analyzer; the hemoglobin value was used to determine anemia status. Data were entered into Epidata Manager, version 4.6.0.2, and analyzed using SPSS Statistical Software, version 25. The independent-sample t-test was used to compare parameters between groups, and correlation statistics was used to correlate parameters between groups. Chi-square was used at a 95% confidence interval, considering P < .05 statistically significant for association among categorical variables. Correlation analysis showed that platelet count was significantly, positively correlated with RBC, and negatively correlated with MCV, MCH, and MCHC (r (P) = 0.168 (.026) and −0.252 (.000), −0.275 (.001), −0.218 (.004), respectively). It was also negatively correlated with HGB and HCT levels in the healthy control (r (P) = −0.266 (.000) and −0.149 (.049) respectively). Morphologically, 44.32% were microcytic hypochromic anemia, 53.98% were normocytic normochromic anemia and 1.70% were macrocytic anemia. The findings showed that platelet count variation correlates well with red cell indices and morphologic types of anemia in adult anemic patients. Such correlation will enable physicians to make diagnoses and administer treatments.
Abdominal pain as a novel manifestation in children with PCDH19-related epilepsy: A case report
Authors: Hu Wandong , Zhao Fen , Ren Ying , Zhang Hongwei , Li Xiaoying
Published: January 2025

Rationale:

PCDH19-related epilepsy manifested various clinical features, including febrile epilepsy, with or without intellectual disability, and psych-behavioral disorders. However, there are few studies demonstrating abdominal pain as the first symptom.

Patient concerns:

A 3-year-old Chinese girl presented with clustered seizures of fever sensitivity accompanied by abdominal pain.

Diagnoses:

After ultrasonography ruled out abdominal organic lesions, electroencephalographic (EEG) identified abdominal pain was a seizure feature. Trio whole-exome sequence demonstrated a de novo and heterozygous PCDH19 missense mutation (NM_001184880: c.824A>G, P.Y275C), which was confirmed by Sanger sequence. The final diagnosis were “PCDH19-related epilepsy; abdominal pain.”

Interventions:

At first, she was treated ineffectively by levetiracetam and valproate. Finally, she was provided with topiramate (TPM).

Outcomes:

The patient had gained seizure-free, and the follow-up EEG discharges were reduced.

Lessons:

Abdominal pain is a rare autonomic symptom in the setting of seizures. This report describes abdominal pain as a novel manifestation of PCDH19-related epilepsy and might expand its phenotypes spectrum. It also alerts us to perceive the abdominal pain characterized by seizures and early conduct EEG examination to clarify the nature of abdominal pain.
Distinct prognostic impacts of age-adjusted Charlson comorbidity index and geriatric nutritional risk index in patients with intraductal papillary mucinous neoplasm
Authors: Yuge Takuya , Murata Yasuhiro , Ito Takahiro , Hayasaki Aoi , Iizawa Yusuke , Fujii Takehiro , Tanemura Akihiro , Kuriyama Naohisa , Kishiwada Masashi , Mizuno Shugo
Published: January 2025

The optimal surgical indication for intraductal papillary mucinous neoplasms (IPMN) remains highly contentious. We aimed to determine the preoperative predictive factors of malignancy and independent prognostic factors in patients with IPMN who underwent curative-intent resection. In this study, 104 patients with a pathological diagnosis of IPMN who underwent curative-intent resection were included. Multivariate regression and Cox proportional-hazards analyses were performed to identify the predictive factors for invasive intraductal papillary mucinous carcinoma (IPMC) and prognostic factors for overall survival (OS) after surgery. Among the 104 patients, 24 (23.1%) were pathologically diagnosed with invasive IPMC, and the remaining 80 had low-grade dysplasia or high-grade dysplasia. The presence of high-risk stigmata was an independent predictive risk factor for invasive IPMC. The age-adjusted Charlson comorbidity index (ACCI) (≥4/<4) and geriatric nutritional risk index (GNRI) (<99/≥99) were independent poor prognostic factors for OS (hazard ratio [HR]: 9.39; 95% confidence interval [CI]: 1.90–46.54; P = .006 and HR: 4.37; 95% CI: 1.07–17.86, P = .040, respectively). Forty patients with ACCI ≥ 4 (38.5%) had a significantly lower 5-year OS rate than those with ACCI < 4 (74.3 vs 98.2%, P < .001). Similarly, 29 patients with GNRI < 99 (27.9%) had a significantly lower 5-year OS rate than those with GNRI ≥ 99 (76.0 vs 95.1%, P < .001). These 2 factors were associated with significantly worse disease-specific survival after surgery.

The ACCI and GNRI emerged as independent prognostic factors after surgery in patients with IPMN. These findings highlight the importance of patient-conditional factors as valuable indicators for predicting favorable long-term survival outcomes after surgery and for facilitating a more precise assessment of surgical eligibility in patients with IPMN.
Development of endosome-related gene signature for the prediction of prognosis and therapeutic response in breast cancer
Authors: Jiang Guowei , Wang Ye
Published: January 2025

Endosomes play a pivotal role in cellular biology, orchestrating processes such as endocytosis, molecular trafficking, signal transduction, and recycling of cellular materials. This study aims to construct an endosome-related gene (ERG)-derived risk signature for breast cancer prognosis. Transcriptomic and clinical data were retrieved from The Cancer Genome Atlas and the University of California Santa Cruz databases to build and validate the model. A Lasso Cox regression model was employed for risk signature construction. The immune landscape was assessed using CIBERSORT and ESTIMATE algorithms, while drug sensitivity was evaluated via the pRRophetic algorithm. Gene set enrichment analysis and gene set variation analysis were applied to evaluate gene expression patterns. A nomogram was constructed and validated for predicting breast cancer outcomes. The expression of ERGs in breast cancer cells and tissues was further validated. Sixty-one ERGs associated with breast cancer prognosis were identified, with 23 selected for constructing the risk signature. This signature stratified breast cancer patients into high- and low-risk groups, where the low-risk group exhibited significantly better prognosis. Notably, younger patients tended to have lower risk scores compared to older ones. The low-risk group exhibited enhanced sensitivity to the majority of the drugs tested, accompanied by increased infiltration of T cells and M1 macrophages. Additionally, cell cycle pathways were suppressed in the low-risk group, whereas antigen binding functions were significantly activated. Ultimately, risk score and age were identified as independent prognostic factors for breast cancer, and these factors were incorporated into a nomogram that demonstrated excellent performance in prognosis assessment. Finally, external cohort validated the dysregulation of the risk score-associated ERGs in breast cancer cells and tissues. This study successfully established an ERG-derived breast cancer risk signature and nomogram, elucidating their potential value in prognosis prediction and evaluation of therapeutic response.
Word-of-mouth referrals between patients are a critical component of medical tourism for pediatric hematopoietic cell transplantation
Authors: Wen Yu-Chuan , Wang Yi-Lun , Pai Lan-Ni , Yang Shu-Ho , Chang Tsung-Yen , Chen Shih-Hsiang , Jaing Tang-Her
Published: January 2025

The increasing popularity of medical tourism has sparked interest from policymakers, researchers, and the media. Factors influencing medical tourism include service quality, availability, economics, and cultural differences. This study aims to analyze the key factors that influence destination selection for medical tourists.

We conducted a thorough examination of hematopoietic cell transplantation (HCT) data from the pediatric population at our institution from 2006 onwards, focusing on the aspect of medical tourism. Most connections to services were made through encounters in patients’ daily lives and environments, such as word-of-mouth (WOM) from previously treated patients, family, or friends; connection through other services; referral from health care professionals; and seeing the service in their neighborhood. The results of our study indicate that the outcomes of these patients were comparable to those of patients with unrelated donor HCT who were not from an international background. Approximately 55% of our patients were referred to those who previously received treatment. Effective WOM referrals between patients are essential to the success of a medical tourism business. Patients referred to hospitals tend to have higher satisfaction rates and are more likely to become repeat customers. This ultimately leads to increased revenue and a stronger reputation in the industry. Additionally, positive feedback from satisfied patients can significantly enhance an organization’s reputation and attract more potential clients. Chinese tourists and Taiwanese people share language and history. Engaging in direct conversations with physicians regarding personal matters has proven to be more effective than depending on the translator. WOM referrals are critical components of the medical tourism industry. The results indicate that WOM referrals play an essential role in conveying patients’ experiences, leading to increased revenue and a stronger reputation in the industry.
Efficacy analysis of acupuncture and rehabilitation for traumatic spinal cord injury
Authors: Jiang Yue-Bo , Guan Ling , Li Ying , Shu Man , Cui Bin-Chuan , Huang Zong-Yue
Published: January 2025

Background:

This study investigates the role and efficacy of acupuncture combined with rehabilitation therapy during the recovery phase of patients with traumatic spinal cord injury. Patients hospitalized in the acupuncture department of our center between December 1, 2019, and December 1, 2021, were enrolled.

Methods:

Participants were divided into an observation group (acupuncture and rehabilitation therapy) and a control group (rehabilitation therapy alone) based on their treatment sequence. Initially, 15 patients were allocated to each group; however, 3 patients in the observation group and 4 in the control group withdrew, leaving 11 and 12 patients in the respective groups. The observation group received combined acupuncture and rehabilitation therapy, while the control group received conventional rehabilitation therapy. Outcomes were evaluated using the American Spinal Injury Association score and classification, urodynamic data, SF-36 scale, Functional Independence Measure, and Barthel Index, analyzed through data mining techniques.

Results:

Posttreatment assessments revealed significant improvements in residual urine volume and detrusor pressure in the observation group (P < .05), whereas no significant changes were noted in the control group (P > .05). Both groups demonstrated improved motor function after treatment (P < .05), with the observation group showing significantly greater improvement (P < .05). Quality of life evaluations indicated substantial enhancement in physical pain, energy levels, general health, social functioning, perceived health changes, and mental health in both groups (P < .05).

Conclusion:

Acupuncture combined with rehabilitation therapy offers significant clinical benefits for patients with traumatic spinal cord injury. This approach effectively alleviates urinary and bowel dysfunction, accelerates motor function recovery, and improves overall quality of life, making it a valuable treatment option worthy of wider adoption.
The impact of workplace bullying on depression among clinical nurses in China: A comparative analysis
Authors: Zhou Jiao-Zhi , Liu Xin , Ye Gong-Jie
Published: January 2025

The objective of this study is to examine the phenomenon of workplace bullying and its potential associations with burnout and depression among clinical nurses in China. A convenience sampling method was utilized to conduct a survey among 415 clinical nurses across 9 hospitals. All questionnaires were completed within a 2-week period in October 2023. The survey questionnaire comprised 3 sections, namely basic information, negative acts questionnaire (NAQ), and self-rating depression scale (SDS). Based on their depression status, the participants were categorized into 2 groups, namely depression group and control group. A comparative analysis of the basic data and NAQ was performed between 2 groups, and factors exhibiting statistically significant differences in the single factor analysis were subjected to binary logistic regression analysis. Additionally, Pearson correlation analysis was utilized to examine the correlations among the variables. Ninety-four individuals were included in depression group, accounting for 22.65% of the total sample, with a mean SDS of 44.7 ± 5.5. The control group consisted of 321 participants, representing 77.35% of the total, with a mean SDS of 24.8 ± 9.0. No statistically significant differences were observed between 2 groups regarding gender, monthly income, education level, night duty, body mass index, working hospital, department, employment status, only child status, local residency, and number of children. The age, length of services, professional title, marital status, and NAQ of depression group and control group were compared, and the difference was found to be statistically significant (P < .05). The findings from the binary logistic regression analysis indicated that both length of service and NAQ emerged as significant independent predictors of nurses’ depression. Furthermore, the results of the Pearson correlation analysis demonstrated a positive association between the depression levels of clinical nurses and NAQ. The duration of employment and NAQ of clinical nurses were independent factors influencing depression. A positive correlation was found between depression and NAQ. It is evident that workplace bullying has a detrimental impact on the mental well-being of clinical nurses. To address this issue, hospital administrators are advised to implement regular psychological clinics for clinical nurses and offer targeted educational programs aimed at increasing awareness of workplace bullying and enhancing coping strategies.
A Neonate Presenting With Large Abdominal Mass: A Rare Case of Congenital Leukemia
Authors: Gaur Bablu K. , Varshney Chirag , Singh Rupa R. , Soneja Prashansa
Published: January 2025

Leukemia symptoms occurring in the first 4 weeks of infancy are known as congenital leukemia. We present a case of congenital leukemia in a full-term neonate manifesting at birth with a grossly distended abdomen due to a large abdominal mass. Ultrasonography of the abdomen showed a large abdominal mass originating from the liver. Congenital leukemia was suspected based on the very high total leukocyte counts and the presence of blast cells in the peripheral blood smear, which was confirmed by bone marrow aspiration. The bone marrow aspirate smear showed 42% blast cells. Due to overwhelming sepsis, the baby died at the neonatal intensive care unit on day 4 after birth. This report highlights the atypical presentations of congenital leukemia in the neonatal period.
A Childhood Langerhans Cell Histiocytosis With a Novel BRAF N486_T491delinsK Mutation: Good Response to Conventional Chemotherapy
Authors: Wan Zhi , Tang Xue , Gao Ju
Published: January 2025

Langerhans cell histiocytosis (LCH) is characterized genetically by diverse gene mutations of the mitogen-activated protein kinase signaling cascade. BRAF

N486_T491delinsK
mutation is a rare mutation that involves the β2-αC ring domain, causing activation of the mitogen-activated protein kinase pathway, and is predicted to be resistant to the chemotherapy and BRAF

V600E
inhibitor in adult LCH cases. Here, we report a childhood LCH case with this novel BRAF mutation and had a good response to conventional chemotherapy. This case report suggests that children with BRAF

N486_T491delinsK
mutation might differ from adult counterparts in terms of clinical behavior, and conventional chemotherapy might still be an effective therapy.
How Does Diploic Space Thickness Change With Age?
Authors: Menville Jesse E. , Shinde Nidhi , Collins Scott , Woo Albert S.
Published: January 2025

Background:

Cranial defects from trauma, surgery, or congenital conditions require precise reconstruction to restore cranial vault integrity. Autogenous calvarial grafts are preferred for their histocompatibility and biomechanical properties, but their success depends on a well-developed diploic space. Although prior studies have described overall skull thickness development, less is known about how diploic thickness changes through adulthood. This study aimed to quantify diploic thickness and density changes with age using computed tomography (CT) imaging.

Methods:

A retrospective review of an institution-wide imaging database was performed to identify patients who received CT scans for non-traumatic indications. A total of 110 patients, balanced by sex, were selected across 11 age groups spanning 10 to 109 years. Each patient’s skull was aligned to a standardized grid and segmented in 3-dimensional (3D) Slicer using consistent thresholding values to isolate the diploic space from the inner and outer cortical tables. Linear regression models were used to assess the effects of age and sex on diploic thickness.

Results:

No statistically significant trends were found between age and diploic thickness (r=−0.06; P=0.50. However, a near-significant trend of decreasing diploic thickness with age was observed in men (r=−0.25; P=0.05) but not in women (r=0.11; P=0.42). The posteromedial parietal region consistently showed the greatest thickness across all age groups. Diploic density also increased significantly with age (r=0.285; P=0.002), indicating progressive ossification of cancellous bone.

Conclusion:

Diploic thickness remains stable across the lifespan with slight sex-based differences. However, examination reveals that the density of the diploe increases over time, suggesting age-related changes in cancellous architecture. These findings highlight the importance of individual anatomical variations when harvesting autogenous calvarial grafts to optimize cranial reconstruction outcomes.
Clinical Outcomes and Donor-specific Antibody Rebound 5 y After Kidney Transplant Enabled by Imlifidase Desensitization
Authors: Jaffe Ian S. , Runström Anna , Tatapudi Vasishta S. , Weldon Elaina P. , Deterville Cecilia L. , Dieter Rebecca A. , Montgomery Robert A. , Lonze Bonnie E. , Mangiola Massimo
Published: January 2025

Background.

Imlifidase is an IgG-cleaving endopeptidase conditionally approved in Europe for desensitization of highly sensitized patients before kidney transplantation. We present 5-y outcomes and donor-specific antibody (DSA) levels for clinical trial participants from a single site who received imlifidase for desensitization before incompatible transplantation (NCT02790437).

Methods.

Imlifidase was administered up to 24 h before living or deceased donor kidney transplantation. DSAs were monitored before transplantation, at days 7 and 28, and at 5 y posttransplant.

Results.

At 5 y, 7 of 8 participants were alive. One of these 7 had suboptimal graft function secondary to donor-derived disease but remained dialysis independent. Three participants had antibody-mediated rejection (AMR), which occurred in the first 30 d in all cases and was successfully treated. No new episodes of suspected or biopsy-proven AMR occurred after 30 d posttransplant. Seven participants had DSA rebound. DSAs commonly persisted 5 y posttransplant, although they were generally lower strength compared with pre-imlifidase. Dilution studies of sensitized serum enabled the identification of lower AMR risk phenotypes for persisting DSAs. Severe and/or opportunistic infections were not observed at greater than expected frequency.

Conclusions.

Five-year outcomes of imlifidase-enabled incompatible transplants are overall favorable. DSA rebound is common, but antibody strength lessens in the long term, and longitudinally persisting DSAs did not lead to premature graft failure.
Effectiveness of Propofol in Mitigation of Emergence Agitation Among Pediatric Patients Undergoing Elective Surgery Under General Anesthesia: Prospective Cohort Study
Authors: Gelgelo Kuchulo Geremu , Tessema Orissa Orkissa , Demissie Wondu Reta , Mekonin Gezahegn Tesfaye
Published: January 2025

Introduction

Emergence agitation is the abnormal mental status that develops as the result of anesthesia administration during the transition from unconsciousness to complete wakefulness. It is more common in pediatrics. It can cause serious life-threatening phenomena. Thus, preventing it would reduce the unwanted side effects and makes emergence smooth.

Objective

Assess effectiveness of propofol in the mitigation of emergence agitation among pediatric patients undergone elective surgery under general anesthesia.

Methods

The study was conducted from October 1/2022 to December 30/ 2022 among pediatric patients aged 2-14 years who underwent elective surgery under general anesthesia. A total of 76 patients were enrolled and grouped into propofol and non-propofol with 38 patients in each. The incidence and severity of EA were assessed.

Statistical analysis was done by SPSS version 26.0. P-value less than 0.05 was taken as statically significant.

Result

The overall incidence of EA in both groups was 48.7% (37%−60.4%). The incidence of EA in the propofol group and non-group was 34.2% (19.6%−51.4%) vs 63.2% (46%−78.2%) respectively p=0.012. There was a significant reduction in the severity of EA at time intervals of 5thand 15thminutes; P =0.012 vs 0.029 respectively. However, there was no significant difference in the severity of EA at the 30thminute between the groups; P=0.08. The RR of EA in the propofol group was 0.542 (95% CI: 0.327-0.896).

Conclusion

The administration prophylactic propofol at the end of surgery is important in reducing both the incidence and severity of emergence agitation.
Vat Photopolymerization of Porous Scaffolds: Stabilization and Layer Thickness Control for Micron-Scale Accuracy
Authors: Chen Guoyao , Ratner Buddy D.
Published: January 2025

Vat Photopolymerization (VPP) holds much promise for producing biomaterial constructs such as porous scaffolds. However, achieving micron-scale pore dimensions with precision presents a challenge. This study offers an innovative approach to stabilize the silicone elastomer vat surface permitting micron-scale layer thickness accuracy to be maintained. Internal and surface contamination on the poly(dimethyl siloxane) (PDMS) vat surface were observed and effectively controlled with a pre-saturation methodology, and porous structures with cubical pores were then printed with varying layer thicknesses. These structures demonstrate the ability to achieve micrometric resolution and layer thicknesses as fine as 32 µm. A scaffold suitable forin vivoimplantation with 40 µm cubical pores was successfully printed within 5 hours using a stabilized PDMS vat surface. Additionally, the methodology’s adaptability to intricate non-linear edge porous structures underscores its versatility across X, Y, and Z-axis.
BellaVista: Open-Source Visualization for Imaging-Based Spatial Transcriptomics
Authors: Coles Annabelle M. , Liu Yuening , Kosuri Pallav
Published: January 2025

Imaging-based spatial transcriptomics can reveal gene expressionin situby locating and identifying individual RNA molecules at subcellular resolution. These datasets typically contain an abundance of information that when analyzed appropriately can reveal tissue organization across scales from molecules to entire organs. However, there is currently a lack of simple open-source tools that facilitate visualization, quality control, and custom spatial analysis.

Here we introduce BellaVista, a lightweight open-source tool for interactive visualization and exploration of imaging-based spatial transcriptomics data. BellaVista natively supports data from Xenium (10x Genomics), MERSCOPE (Vizgen), and custom MERFISH platforms. By providing a simple means for simultaneous visualization of images, transcripts, and cell segmentation boundaries, we anticipate that BellaVista will accelerate accessibility, exploration and discovery in the rapidly expanding field of spatial biology. BellaVista is available athttps://github.com/pkosurilab/BellaVista.
Dioecy in a wind-pollinated herb explained by disruptive selection on sex allocation
Authors: Chen Kai-Hsiu , Pannell John R
Published: January 2025

The evolution of dioecy from hermaphroditism is widely thought to be a response to disruptive selection favouring males and females, driven by advantages of inbreeding avoidance, sexual specialisation, or both. However, it has hitherto been difficult to uncouple the importance of these two advantages of dioecy. Here, we estimate the selfing rate and fitness gain curves with and without inbreeding depression in wind-pollinated Mercurialis annua, based on variation in sex allocation among hermaphrodites that evolved from dioecy following the experimental removal of males. Because males had been removed, we could rule out any important contribution to disruptive selection due to advantages of sexual specialisation, allowing us to focus in inbreeding effects. Our results confirm a tradeoff between male and female allocation in M. annua, as assumed in sex-allocation theory. The individual selfing rates increased with male allocation, greatly altering the female and male fitness gain curves under strong inbreeding depression. There was strong disruptive selection on sex allocation due to its interaction with the mating system. Taken together, our study demonstrates that inbreeding avoidance on its own can lead to disruptive selection on sex allocation and thus the selection and maintenance of dioecy under wind pollination.
Restrictor slows early transcription elongation to render RNA polymerase II susceptible to termination at non-coding RNA loci
Authors: Mimoso Claudia A. , Vlaming Hanneke , de Wagenaar Nathalie P. , Adelman Karen
Published: January 2025

The eukaryotic genome is broadly transcribed by RNA polymerase II (RNAPII) to produce protein-coding messenger RNAs (mRNAs) and a repertoire of non-coding RNAs (ncRNAs). Whereas RNAPII is very processive during mRNA transcription, it terminates rapidly during synthesis of many ncRNAs, particularly those that arise opportunistically from accessible chromatin at gene promoters or enhancers. The divergent fates of mRNA versus ncRNA species raise many questions about how RNAPII and associated machineries discriminate functional from spurious transcription. The Restrictor complex, comprised of the RNA binding protein ZC3H4 and RNAPII-interacting protein WDR82, has been implicated in restraining the expression of ncRNAs. However, the determinants of Restrictor targeting and the mechanism of transcription suppression remain unclear. Here, we investigate Restrictor using unbiased sequence screens, and rapid protein degradation followed by nascent RNA sequencing. We find that Restrictor promiscuously suppresses early elongation by RNAPII, but this activity is blocked at most mRNAs by the presence of a 5’ splice site. Consequently, Restrictor is a critical determinant of transcription directionality at divergent promoters and prevents transcriptional interference. Finally, our data indicate that rather than directly terminating RNAPII, Restrictor acts by reducing the rate of transcription elongation, rendering RNAPII susceptible to early termination by other machineries.
Distinct origin and fate for fetal hematopoietic progenitors
Authors: Soares-da-Silva F. , Nogueira G. , Mailhe Marie-Pierre , Freyer L. , Perkins A. , Hatano S. , Yoshikai Y. , Pereira P. , Bandeira A. , Elsaid R. , Gomez-Perdiguero E. , Cumano A.
Published: January 2025

It was proposed that two sequential sources of intraembryonic multipotent progenitors ensure blood cell production from late gestation into adulthood, with only the latter producing self-renewing hematopoietic stem cells (HSC). How these two populations differ and how they impact the establishment of the postnatal immune system, remains poorly understood. Using complementary lineage tracing models, we showed that the first emerging embryonic multipotent progenitors (eMPP) are responsible for late gestation hematopoiesis. They are distinct from HSC that do not significantly contribute to embryonic mature blood cells. eMPP are the predominant source of embryonic lymphocytes and lymphoid tissue inducer cells, some of which persist for life. Between E12.5 and E16.5 eMPP rapidly differentiate, whereas HSC expand 20-fold. Altogether, these results support the notion that eMPP establish the embryonic adaptive immune system and shape the lymphoid organs where later adaptive immune responses occur, while HSC expand to sustain blood cell production throughout life.
Optimization of Extraction Process by Response Surface Method-ology of Total Flavonoids fromZiziphus JujubeFlesh and its Sedative-Hypnotic Effects
Authors: Li Jie , Li Baojian , Shi Xinbo , Yang Yuangui , Song Zhongxing
Published: January 2025

Background & aims

This study optimizes the extraction process of total flavonoids fromZiziphus jujubeflesh (TFZJF) by response surface methodology and investigating its sedative-hypnotic effects and mechanisms in a para-chlorophenylalanine (PCPA)-induced insomnia mouse model. It provides theoretical support for the further comprehensive utilization ofZiziphus jujubefruit and flesh.

Methods

Single-factor experiment and Box–Behnken response surface design were used to study the ethanol reflux extraction process of TFZJF, with flavonoid extraction rate as the indicator, to obtain the optimal extraction process of TFZJF. An insomnia model in mice was induced via an intraperitoneal injection of PCPA, and the effects of TFZJF on this model, along with its underlying mechanisms, were assessed using various approaches, including sodium pentobarbital-induced sleep potentiation, HE staining of tissue sections, ELISA, RT-PCR, WB, and serum metabolomics.

Results

The results showed that the optimized extraction conditions for TFZJF included a solid–liquid ratio (SLR) of 1:25 g·mL⁻1, ethanol concentration of 60%, and extraction time of 60 min, yielding an extraction efficiency of 1.98%. Data from the experimental groups indicated dose-dependent sleep improvement in the insomnia model, with the high-dose TFZJF (TFZJF-H) group exhibiting the most significant effect, followed by the medium-dose (TFZJF-M) and low-dose (TFZJF-L) groups. Metabolomic analysis revealed that TFZJF administration positively impacted the metabolic profile of PCPA-induced insomnia, particularly affecting pathways related to phenylalanine, tyrosine, cytochrome P450, and alanine metabolism on non-targeted metabolomics.

Conclusions

The extraction process is stable and reliable, which can be used for the extraction of TFZJF; meanwhile, TFZJF demonstrated significant sleep-enhancing effects in the PCPA-induced insomnia mouse model, supporting its potential for resource development and the utilization of non-medicinal parts ofZiziphus jujube.
Ordered release of genomic RNA during icosahedral virus disassembly
Authors: Zhou Yiyang , Routh Andrew L.
Published: January 2025

To release their genomic cargo, many icosahedral viruses undergo a series of ordered conformational changes via distinct disassembly intermediates that allow nucleic acid egress. Previous studies have focused on the rearrangement of the virus capsid protein shell during disassembly. However, it is unclear whether the packaged viral nucleic acids also undergo defined rearrangements or whether specific regions of the viral genome are released in a predetermined order. In this study, we established a Next-Generation Sequencing platform (“PT-ClickSeq”) that does not require RNA extraction or fragmentation and so can natively sequence the nucleic acid exposed during virus particle disassembly without disrupting the capsid protein. We used Flock House virus (FHV) as a model system, which produces two well-defined disassembly intermediates with externalized RNA. With PT-ClickSeq, we found that FHV releases RNA genome in an ordered and conserved fashion with the 5’ and 3’ terminal regions of viral genomic RNAs and specific loci within the viral genome being released first during virus particle disassembly. Further, different genomic loci exhibit distinct energy barriers prior to release, suggesting a programmed exposure of the viral RNA. We also characterized viral RNA-capsid interactions using established cross-linking and NGS approaches (“vPAR-CL”) and observed a disordering of RNA-capsid interactions during disassembly. Interestingly, we noticed an anti-correlation between preferentially released RNA regions and strong RNA-capsid interactions observed prior to disassembly. These findings demonstrate that rather than being a passive cargo, the encapsidated viral genome serves an important role in programmed virus disassembly.

Significance

Viruses need to strike a balance between structural rigidity and flexibility, to achieve both sufficient protection and rapid release of packaged genome into host cells. During the process of genome delivery, many viruses undergo a programed disassembly process through successive morphological changes, which give rise to partially dissembled virus particles, termed disassembly intermediates. It is important to study these intermediates as “checkpoints” to understand virus disassembly dynamics. We established a next-generation sequencing method that can monitor the RNA behavior during these conformational changes. We found that different regions of RNA were released with different energy thresholds and the RNA release prioritized regions with low RNA-protein interactions. These findings shed light on the active role of the viral RNA in virus disassembly.
LINE-1, the NORth star of nucleolar organization
Authors: Matsuo Misaki , Cristofari Gael
Published: January 2025

Long interspersed element-1 (LINE-1) retrotransposons are abundant transposable elements in mammals and significantly influence chromosome structure, chromatin organization, and 3D genome architecture. In this issue ofGenes & Development, Ataei et al. (doi:10.1101/gad.351979.124) identify a homininae-specific LINE-1 element within nucleolar organizer regions (NORs) that is specifically transcribed in naïve human embryonic stem cells. Deletion or silencing of this element disrupts nucleolar organization and function and alters cellular identity. These findings provide novel insights into the role of retrotransposons in genome organization and suggest that individual LINE-1 elements may have evolved specialized roles.
Weak interaction axial form factors of the octet baryons in nuclear medium
Authors: Ramalho G. , Tsushima K. , Cheoun Myung-Ki
Published: January 2025

We study the axial-vector and the induced pseudoscalar form factors associated with the weak transitions between the octet baryon members in nuclear medium, using a covariant constituent quark model. We extend previous calculations of the axial transition form factors from the vacuum (free space) to the nuclear medium (symmetric nuclear matter). The extension of the model to the nuclear medium takes into account the modifications of the properties of hadrons in the medium (masses and coupling constants), as determined by the quark-meson coupling model. The axial-vector (GA) and the induced pseudoscalar (GP) form factors are evaluated for different values of the nuclear density ρ in terms of the square transfer momentum q2=−Q2. We conclude that, in general, the GA and GP form factors are reduced in the nuclear medium. The reduction is stronger for light baryons and high densities. The medium modifications are milder for the heavier octet baryons, particularly at large Q2. The calculations presented here can be used to estimate the cross sections of neutrino and antineutrino scattering with nucleus, and neutrino and antineutrino scattering with hyperons bound to a nucleus, as well as those in the cores of compact stars.

Published by the American Physical Society
2025
Constraints on the maximal number of dark degrees of freedom from black hole evaporation, cosmic rays, colliders, and supernovae
Authors: Ewasiuk Chris , Profumo Stefano
Published: January 2025

A dark sector with a very large number of massive degrees of freedom is generically constrained by radiative corrections to Newton’s constant. However, there are caveats to this statement, especially if the degrees of freedom are light or massless. Here, we examine in detail and update a number of constraints on the possible number of dark degrees of freedom, including from black hole evaporation, from perturbations to systems including an evaporating black hole, from direct gravitational production at colliders, from high-energy cosmic rays, and from supernovae energy losses.

Published by the American Physical Society
2025