bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between triglyceride-glucose index baselines and trajectories with incident cardiovascular diseases in the elderly population
Authors: Wang Yue , Chen Xueyu , Shi Jie , Du Mingyi , Li Shengnan , Pang Jinhong , Qiao Junpeng , Zhao Yingying , Chen Qiaoqiao , Guo Yuanyuan , Xi Yan , Chi Weiwei
Published: January 2024

Background

The triglyceride-glucose (TyG) index is regarded as a sophisticated surrogate biomarker for insulin resistance, offering a refined means for evaluating cardiovascular diseases (CVDs). However, prospective cohort studies have not simultaneously conducted baseline and multi-timepoint trajectory assessments of the TyG index in relation to CVDs and their subtypes in elderly participants.

Methods

After excluding data deficiencies and conditions that could influence the research outcomes, this study ultimately incorporated a cohort of 20,185 participants, with data chronicles extending from 2016 to 2022. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Latent Class Trajectory Model (LCTM) was used to assess the change trends of the TyG index over multiple time points. Utilizing the Cox proportional-hazards models, we assessed the relationship between the baseline quartiles of the TyG index and various trajectories with CVDs and subtypes.

Results

During the mean follow-up time of 4.25 years, 11,099 patients experienced new CVDs in the elderly population. After stratifying by baseline TyG quartiles, the higher TyG level was associated with an increased risk of CVDs; the aHR and 95% CI for the highest quartile group were 1.28 (1.19–1.39). Five trajectory patterns were identified by the LCTM model. The low gradual increase group as the reference, the medium stable group, and the high gradual increase group exhibited an elevated risk of CVDs onset, aHR and 95%CIs were 1.17 (1.10–1.25) and 1.25 (1.15–1.35). Similar results were observed between the trajectories of the TyG index with subtypes of CVDs.

Conclusion

Participants with high levels of baseline TyG index and medium stable or high gradual increase trajectories were associated with an elevated risk of developing CVDs in elderly populations.
Development of a genetic engineering toolbox for syngas-utilizing acetogen Clostridium sp. AWRP
Authors: Kwon Hae Jun , Lee Joungmin , Kwon Soo Jae , Lee Hyun Sook
Published: January 2024

Background

Clostridium sp. AWRP (AWRP) is a novel acetogenic bacterium isolated under high partial pressure of carbon monoxide (CO) and can be one of promising candidates for alcohol production from carbon oxides. Compared to model strains such as C. ljungdahlii and C. autoethanogenum, however, genetic manipulation of AWRP has not been established, preventing studies on its physiological characteristics and metabolic engineering.

Results

We were able to demonstrate the genetic domestication of AWRP, including transformation of shuttle plasmids, promoter characterization, and genome editing. From the conjugation experiment with E. coli S17-1, among the four replicons tested (pCB102, pAMβ1, pIP404, and pIM13), three replicated in AWRP but pCB102 was the only one that could be transferred by electroporation. DNA methylation in E. coli significantly influenced transformation efficiencies in AWRP: the highest transformation efficiencies (102–103 CFU/µg) were achieved with unmethylated plasmid DNA. Determination of strengths of several clostridial promoters enabled the establishment of a CRISPR/Cas12a genome editing system based on Acidaminococcus sp. BV3L6 cas12a gene; interestingly, the commonly used CRISPR/Cas9 system did not work in AWRP, although it expressed the weakest promoter (C. acetobutylicum Pptb) tested. This system was successfully employed for the single gene deletion (xylB and pyrE) and double deletion of two prophage gene clusters.

Conclusions

The presented genome editing system allowed us to achieve several genome manipulations, including double deletion of two large prophage groups. The genetic toolbox developed in this study will offer a chance for deeper studies on Clostridium sp. AWRP for syngas fermentation and carbon dioxide (CO2) sequestration.
Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study
Authors: Wang Xiaoyan , Miao Shuchuan , Yang Yuanwei , Yang Qilin , Meng Dejiao , Liang Hong
Published: January 2024

Background

Whether early dietary fiber intake in septic patients is associated with a better clinical prognosis remains unclear, especially the time and the amount. Therefore, we assessed the association between early dietary fiber intake and clinical outcomes in septic patients by examining an extensive database.

Methods

We conducted a retrospective cohort study using data from the MIMIC IV 2.1 database, focusing on consecutive septic patients requiring mechanical ventilation in medical or mixed medical-surgical ICUs. We collected patient demographics and nutritional data. Dietary fiber amounts were calculated according to enteral nutrition instructions from manufacturers within the first 72 h after admission. After adjusting for covariates, we employed restricted cubic spline (RCS) regression to investigate the relationship between fiber intake (FI) and 28-day mortality. Patients were categorized into three groups based on their fiber index (FI) within 72 h of admission: low fiber index (LFI) group when FI was < 3 g/(%), medium fiber index (MFI) group when FI ranged from 3 to 35 g(%), and high fiber index (HFI) group when FI ≥ 35 g(%). Univariate and multivariate Cox proportional hazards regression models were utilized to assess the association between early FI and 28-day mortality. We ultimately employed Kaplan–Meier (KM) curves and log-rank test visually represent the association between FI and 90-day mortality. The second outcomes include ICU-acquired infections and the hospital and ICU death, length of hospital and ICU stay, and length of mechanical ventilation.

Results

Among 1057 subjects, 562 (53.2%) were male, with a median age of 64.8 years (IQR 53.4–75.2). We observed a J-shaped relationship between FI and 28-day mortality. The MFI group exhibited the lowest 28-day mortality [adjusted HR 0.64 (0.45–0.91), p = 0.013] and the lowest rate of hospital mortality [adjusted OR 0.60 (0.39–0.93), p = 0.022], with no statistically significant differences noted in the HFI group when compared to the LFI group. Similar patterns were observed for 60-day and 90-day mortality. However, no statistically significant differences were observed in other secondary outcomes after adjusting for covariates.

Conclusion

Early medium fiber index intake improved 28-day mortality and lower hospital mortality in septic M/SICU patients on mechanical ventilation.
The effect of diet-induced weight loss on circulating homocysteine levels in people with obesity and type 2 diabetes
Authors: Al Fatly Meryem , Mulder Monique T. , Roeters van Lennep Jeanine , Blom Henk J. , Berk Kirsten A.C.
Published: January 2024

Background/aims

Having type 2 diabetes (T2D) in combination with being overweight results in an additional increase in cardiovascular disease (CVD) risk. In addition, T2D and obesity are associated with increased levels of total homocysteine (tHcy), possibly contributing to the CVD risk. Weight loss dieting has positive effects on several CVD risk factors, but whether it affects tHcy remains unclear. Therefore, the aim of this study was to determine the effect of a calorie restricted diet on tHcy in overweight people with T2D.

Methods

In this post-hoc analysis of the POWER study, adults with T2D and a BMI greater than 27 kg/m² were included from the outpatient diabetes clinic of the Erasmus Medical Center, Rotterdam. The patients were subjected to a very low-calorie diet with fortified meal replacements for 20 weeks. Before and after this intervention, blood samples were collected to measure tHcy and other CVD risk factors like glycaemic and lipid parameters.

Results

161 overweight participants with T2D were included, with a mean age of 54 years (range 26–74), mean weight of 104.6 ± 19.9 kg and mean HbA1c of 62.7 ± 14.3 mmol/mol. At baseline, men displayed higher tHcy than women, and tHcy level was positively correlated with body weight and triglyceride levels, while it was negatively correlated with renal function and HDL cholesterol. During the intervention, bodyweight was reduced by a mean of 9.7% (from 104.6 ± 19.9 to 94.5 ± 18.1 kg p < 0.001), and all measured glycaemic and lipid blood parameters improved significantly. However, tHcy remained unchanged (from 12.1 ± 4.1 to 12.1 ± 4.2 umol/L, p = 0.880). The change in tHcy during the intervention was negatively associated with the change in weight and BMI (p = 0.01 and p = 0.008, respectively). People who lost < 10 kg (n = 92) had a mean tHcy change of -0.47 umol/L, while people who lost more than ≥ 10 kg (n = 69) had a mean tHcy change of 0.60 umol/L (p = 0.021).

Conclusion

In conclusion, our data show that a calorie restricted diet does not affect tHcy in people with T2D and obesity, despite the use of meal replacements fortified with folic acid and vitamin B12. Our data showed a negative correlation between change in tHcy levels and weight loss, suggesting that people who lost more weight (> 10 kg) showed an increase in tHcy. Future studies should explore the potential increase in tHcy induced by weight loss dieting and target the question if tHcy reduction strategies during weight loss could be clinically beneficial.
Exposure to cadmium and lead is associated with diabetic kidney disease in diabetic patients
Authors: Zhang Yuan , Gong Xiaoyu , Li Runhong , Gao Wenhui , Hu Daibao , Yi Xiaoting , Liu Yang , Fang Jiaxin , Shao Jinang , Ma Yanan , Jin Lina
Published: January 2024

Background

Cadmium (Cd) and lead (Pb) exhibit nephrotoxic activity and may accelerate kidney disease complications in diabetic patients, but studies investigating the relation to diabetic kidney disease (DKD) have been limited. We aimed to examine the associations of Cd and Pb with DKD in diabetic patients.

Methods

3763 adults with blood metal measurements and 1604 adults with urinary ones who were diabetic from National Health and Nutrition Examination Survey (NHANES) 2007–2016 were involved. Multivariate logistic regression models were used to analyze the associations of blood Cd (BCd), blood Pb (BPb), urinary Cd (UCd), and urinary Pb (UPb) with DKD.

Results

BPb, BCd, and UCd levels were higher among participants with DKD than diabetics without nephropathy, but UPb performed the opposite result. BPb and UCd were significantly associated with DKD in the adjusted models (aOR, 1.17 (1.06, 1.29);1.52 (1.06, 2.02)). Participants in the 2nd and 3rd tertiles of BPb and BCd levels had higher odds of DKD, with a significant trend across tertiles, respectively (all P-trend < 0.005). Multiplication interaction was also identified for BPb and BCd (P for interaction = 0.044).

Conclusion

BPb, BCd, and UCd were positively associated with the risk of DKD among diabetic patients. Furthermore, there were the dose-response relationship and multiplication interaction in the associations of BPb, BCd with DKD.
Synergistic vesicle-vector systems for targeted delivery
Authors: Marquez Christine Ardelle , Oh Cho-Im , Ahn Gna , Shin Woo-Ri , Kim Yang-Hoon , Ahn Ji-Young
Published: January 2024

With the immense progress in drug delivery systems (DDS) and the rise of nanotechnology, challenges such as target specificity remain. The vesicle-vector system (VVS) is a delivery system that uses lipid-based vesicles as vectors for a targeted drug delivery. When modified with target-probing materials, these vesicles become powerful vectors for drug delivery with high target specificity. In this review, we discuss three general types of VVS based on different modification strategies: (1) vesicle-probes; (2) vesicle-vesicles; and (3) genetically engineered vesicles. The synthesis of each VVS type and their corresponding properties that are advantageous for targeted drug delivery, are also highlighted. The applications, challenges, and limitations of VVS are briefly examined. Finally, we share a number of insights and perspectives regarding the future of VVS as a targeted drug delivery system at the nanoscale.

Graphical Abstract
Laparoscopic hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: a systematic review and meta-analysis
Authors: Xiang Zhi-qiang , Wu Ya-chen , Qu Xi-lin , Luo Dan-jie , Liang Hao , Ameer Sajid , Long Zhang-tao , Dai Xiao-ming , Zhu Zhu
Published: January 2024

Objective

To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH).

Methods

A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals.

Results

Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival.

Conclusions

HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients.
A review of combined functional neuroimaging and motion capture for motor rehabilitation
Authors: Lorenz Emanuel A. , Su Xiaomeng , Skjæret-Maroni Nina
Published: January 2024

Background

Technological advancements in functional neuroimaging and motion capture have led to the development of novel methods that facilitate the diagnosis and rehabilitation of motor deficits. These advancements allow for the synchronous acquisition and analysis of complex signal streams of neurophysiological data (e.g., EEG, fNIRS) and behavioral data (e.g., motion capture). The fusion of those data streams has the potential to provide new insights into cortical mechanisms during movement, guide the development of rehabilitation practices, and become a tool for assessment and therapy in neurorehabilitation.

Research objective

This paper aims to review the existing literature on the combined use of motion capture and functional neuroimaging in motor rehabilitation. The objective is to understand the diversity and maturity of technological solutions employed and explore the clinical advantages of this multimodal approach.

Methods

This paper reviews literature related to the combined use of functional neuroimaging and motion capture for motor rehabilitation following the PRISMA guidelines. Besides study and participant characteristics, technological aspects of the used systems, signal processing methods, and the nature of multimodal feature synchronization and fusion were extracted.

Results

Out of 908 publications, 19 were included in the final review. Basic or translation studies were mainly represented and based predominantly on healthy participants or stroke patients. EEG and mechanical motion capture technologies were most used for biomechanical data acquisition, and their subsequent processing is based mainly on traditional methods. The system synchronization techniques at large were underreported. The fusion of multimodal features mainly supported the identification of movement-related cortical activity, and statistical methods were occasionally employed to examine cortico-kinematic relationships.

Conclusion

The fusion of motion capture and functional neuroimaging might offer advantages for motor rehabilitation in the future. Besides facilitating the assessment of cognitive processes in real-world settings, it could also improve rehabilitative devices’ usability in clinical environments. Further, by better understanding cortico-peripheral coupling, new neuro-rehabilitation methods can be developed, such as personalized proprioceptive training. However, further research is needed to advance our knowledge of cortical-peripheral coupling, evaluate the validity and reliability of multimodal parameters, and enhance user-friendly technologies for clinical adaptation.
Unexpected thermal stability of two enveloped megaviruses, Emiliania huxleyi virus and African swine fever virus, as measured by viability PCR
Authors: Balestreri Cecilia , Schroeder Declan C. , Sampedro Fernando , Marqués Guillermo , Palowski Amanda , Urriola Pedro E. , van de Ligt Jennifer L. G. , Yancy Haile F. , Shurson Gerald C.
Published: January 2024

Background

The particle structure of Emiliania huxleyi virus (EhV), an algal infecting member of nucleocytoplasmic large DNA viruses (NCLDVs), contains an outer lipid membrane envelope similar to that found in animal viruses such as African swine fever virus (ASFV). Despite both being enveloped NCLDVs, EhV and ASFV are known for their stability outside their host environment.

Method

Here we report for the first time, the application of a viability qPCR (V-qPCR) method to describe the unprecedented and similar virion thermal stability of both EhV and ASFV. This result contradicts the cell culture-based assay method that suggests that virus “infectivity” is lost in a matter of seconds (for EhV) and minutes (for ASFV) at temperature greater than 50 °C. Confocal microscopy and analytical flow cytometry methods was used to validate the V-qPCR data for EhV.

Results

We observed that both EhV and ASFV particles has unprecedented thermal tolerances. These two NCLDVs are exceptions to the rule that having an enveloped virion anatomy is a predicted weakness, as is often observed in enveloped RNA viruses (i.e., the viruses causing Porcine Reproductive and Respiratory Syndrome (PRRS), COVID-19, Ebola, or seasonal influenza). Using the V-qPCR method, we confirm that no PRRSV particles were detectable after 20 min of exposure to temperatures up to 100 °C. We also show that the EhV particles that remain after 50 °C 20 min exposure was in fact still infectious only after the three blind passages in bioassay experiments.

Conclusions

This study raises the possibility that ASFV is not always eliminated or contained after applying time and temperature inactivation treatments in current decontamination or biosecurity protocols. This observation has practical implications for industries involved in animal health and food security. Finally, we propose that EhV could be used as a surrogate for ASFV under certain circumstances.
A novel missense COL9A3 variant in a pedigree with multiple lumbar disc herniation
Authors: Jiang Lejian , Wang Chenhuan , Ye Zhaoming , Hu Qingfeng
Published: January 2024

Trp3 allele in COL9A3 gene has been widely studied in populations with intervertebral disc disease. We identified a novel pathogenic variant in COL9A3 gene in a pedigree with multiple lumbar disc herniation (LDH). The proband was a 14-year-old boy who developed LDH at the L4/5 and L5/S1 spinal segments. His father, paternal aunt and grandfather were diagnosed with LDH at an age of 35, 30 and 23, respectively. By applying whole exome sequencing, a heterozygous missense variant (c.1150C > T, p.Arg384Trp) in COL9A3 was identified. According to the ACMG guidelines, this variant is predicted to be pathogenic. In addition, prediction tools found COL9A3 protein of this variant a reduced stability, some changed charge properties, and an altered spatial conformation. Findings expanded the mutational spectrum of LDH and contributed to the understanding of COL9A3 in the pathogenesis of LDH.
Baicalin inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes by activating Nrf-2 signaling pathway
Authors: Liu Jiuxiang , Zhou Hao , Chen Jiangqi , Zuo Qiang , Liu Feng
Published: January 2024

Background

Osteoarthritis (OA) is a common degenerative disease involving articular cartilage, in which ferroptosis of chondrocytes plays an important role. Baicalin (BAI) exerts regulatory effects in a wide range of orthopedic diseases including OA, but its effect on ferroptosis of chondrocytes (CHs) is still unclear. The purpose of this study was to determine the effect of BAI on ferroptosis in human OA chondrocytes (OACs), and to explore its possible mechanism.

Methods

CHs were treated with IL-1β (10 ng/mL) to simulate inflammation in vitro. Immunofluorescence, quantitative RT-PCR, Western blotting and cell viability assay were performed to evaluate the impacts of BAI on Fe2+ level, mitochondrial dysfunction, ferroptosis-related proteins, oxidative stress and cytotoxicity in CHs. Additionally, siRNA was made use of to knock out nuclear factor E2-related factor 2 (Nrf2) to analyze the role played by Nrf2 in BAI-induced CH ferroptosis.

Results

BAI eliminated IL-1β-induced Fe2+ accumulation, changes in mitochondrial membrane potential and ferroptosis-related protein GPX4, SLC7A11, P53 and ACSL4 levels, as well as reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) accumulation in CHs. Besides, BAI reversed IL-1β-induced decrease of Collagen II and increase of MMP13 in CHs. Meanwhile, BAI attenuated IL-1β-induced CH toxicity and promoted Nrf2 antioxidant system activation. When Nrf2 was knocked down by siRNA, the effects of BAI on IL-1β-induced ferroptosis-related proteins and antioxidant stress in CHs were significantly weakened.

Conclusions

This study demonstrates that IL-1β can induce CH ferroptosis. BAI is able to inhibit IL-1β-induced CH ferroptosis and ECM degradation, and the specific mechanism may be that it can inhibit IL-1β-induced CH ferroptosis by activating Nrf2 antioxidant system to attenuate the accumulation of intracellular ROS and lipid ROS.
The effect of preoperative different dexamethasone regimens on postoperative glycemic control in patients with type 2 diabetes mellitus undergoing total joint arthroplasty: a retrospective cohort study
Authors: Mou Ping , Zhao Xiao-Dan , Cai Xin-Yu , Liu Zun-Han , He Cheng-Qi
Published: January 2024

Background

Concerns have been raised regarding the impact of preoperative intravenous dexamethasone on postoperative glycemic control in diabetic patients undergoing total joint arthroplasty (TJA). This study aimed to determine relationships between preoperative different dexamethasone regimens and postoperative fasting blood glucose (FBG), as well as to identify risk factors for postoperative FBG ≥ 200 mg/dl in diabetic patients undergoing TJA.

Methods

This retrospective study included 1216 diabetic patients undergoing TJA and categorized into group A (dexamethasone = 0 mg), group B (dexamethasone = 5 mg), and group C (dexamethasone = 10 mg). All dexamethasone was administered before skin incision. FBG levels were monitored until postoperative day (POD) 3. Analyses were conducted for periprosthetic joint infection (PJI) and wound complications during 90 days postoperatively. And the risk factors for postoperative FBG ≥ 200 mg/dl were identified.

Results

Preoperative dexamethasone administration resulted in a transiently higher FBG on POD 0 and POD 1 (all P < 0.001). However, no differences were observed on POD 2 (P = 0.583) and POD 3 (P = 0.131) among three groups. While preoperative dexamethasone led to an increase in postoperative mean FBG and postoperative maximum FBG (all P < 0.001), no differences were found in wound complications (P = 0.548) and PJI (P = 1.000). Increased HbA1c and preoperative high FBG, but not preoperative dexamethasone, were identified as risk factors for postoperative FBG ≥ 200 mg/dl. Preoperative HbA1c level of ≥ 7.15% was associated with an elevated risk of postoperative FBG ≥ 200 mg/dl.

Conclusions

Although preoperative intravenous administration of 5 mg or 10 mg dexamethasone in diabetic patients showed transient effects on postoperative FBG after TJA, no differences were found in the rates of PJI and wound complications during 90 days postoperatively. Notably, patients with a preoperative HbA1c level of ≥ 7.15% and elevated preoperative FBG may encountered postoperative FBG ≥ 200 mg/dl.
Nomogram based on high-density lipoprotein cholesterol for the occurrence of preoperative deep vein thrombosis in patients with intertrochanteric femur fracture: a retrospective study
Authors: Li Wencai , Ling He , Lu Rongbin , Huang Zhao , Su Wei
Published: January 2024

Background

This study aims to develop a nomogram and forecast the incidence of DVT in individuals suffering from an intertrochanteric femur fracture.

Method

This work created a nomogram using the R programming language and employed logistic regression to determine independent predicting features. An external validation dataset was used to validate the nomogram.

Result

The findings demonstrated the independence of LYM (0.02[0.01–0.09], p < 0.001), ALB (0.83[0.74, 0.94], p = 0.002), and HDL-C (0.18[0.04, 0.71], p = 0.014). Good prediction performance with modest errors was shown by the nomogram in both the training and validation groups.

Conclusion

In conclusion, the nomogram that was created using HDL-C, ALB, and LYM can assist medical professionals in determining the likelihood that DVT will occur.
Robotic-assisted right upper lobectomy with systemic pulmonary vein anomaly: a case report
Authors: Liu Wenwu , Xie Shaohua , Zhang Kaixin , Zhao Yingzhi , Gao Xin , Dai Wei , Shi Qiuling , Hu Bin , Li Qiang , Wei Xing
Published: January 2024

Background

While the role of low-dose computed tomography (CT) in lung cancer screening is established, its limitations in detailing pulmonary vascular variations are less emphasized. Three-dimensional reconstruction technology allows surgeons to reconstruct a patient’s bronchial and pulmonary vascular structures using CT scan results. However, low-dose CT may not provide the same level of clarity as enhanced CT in displaying pulmonary vascular details. This limitation can be unfavorable for preoperative detection of potential pulmonary vascular variations, especially in cases involving planned segmentectomy.

Case Presentation

We report a case of a 58-year-old female with lung cancer, initially planned for Da Vinci robot-assisted thoracoscopic segmentectomy. Unexpectedly, during surgery, a pulmonary vein variation in the right upper lobe was discovered, leading to a change in the surgical method to a lobectomy. The patient had four variant right upper lobe veins draining into the superior vena cava and one into the left atrium. The surgery was complicated by significant bleeding and postoperative pulmonary congestion. Postoperative pathology confirmed adenocarcinoma.

Conclusions

This case highlights the importance of meticulous intraoperative exploration, particularly in cases involving planned segmentectomy, as unexpected pulmonary vein variations can significantly affect surgical decision-making. While three-dimensional reconstruction based on preoperative CT data is a valuable tool, it may not capture the full complexity of the anatomical variations. We discuss potential preoperative imaging techniques, including contrast-enhanced CT and CT angiography, as methods to better identify these variations. The enhanced visualization provided by robot-assisted surgery plays a crucial role in identifying and adapting to these variations, underscoring the advantages of this surgical approach. Our report contributes to the existing literature by providing a detailed account of how these principles were applied in a real-world scenario, reinforcing the need for surgical adaptability and awareness of the limitations of low-dose CT in complex cases.
Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer’s disease
Authors: Wang Lihua , Nykänen Niko-Petteri , Western Daniel , Gorijala Priyanka , Timsina Jigyasha , Li Fuhai , Wang Zhaohua , Ali Muhammad , Yang Chengran , Liu Menghan , Brock William , Marquié Marta , Boada Mercè , Alvarez Ignacio , Aguilar Miquel , Pastor Pau , Ruiz Agustín , Puerta Raquel , Orellana Adelina , Rutledge Jarod , Oh Hamilton , Greicius Michael D , Le Guen Yann , Perrin Richard J. , Wyss-Coray Tony , Jefferson Angela , Hohman Timothy J. , Graff-Radford Neill , Mori Hiroshi , Goate Alison , Levin Johannes , Sung Yun Ju , Cruchaga Carlos
Published: January 2024

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an epistatic effect for sTREM2 levels and AD risk. The novel TREM2 locus on chr 6 contains two rare missense variants (rs75932628 p.R47H, P=7.16×10-19; rs142232675 p.D87N, P=2.71×10-10) associated with sTREM2 and AD risk. The third novel locus in the TGFBR2 and RBMS3 gene region (rs73823326, P=3.86×10-9) included a regulatory variant with a microglia-specific chromatin loop for the promoter of TGFBR2. Using cell-based assays we demonstrate that overexpression and knock-down of TGFBR2, but not RBMS3, leads to significant changes of sTREM2. The last novel locus is located on the APOE region (rs11666329, P=2.52×10-8), but we demonstrated that this signal was independent of APOE genotype. This signal colocalized with cis-eQTL of NECTIN2 in the brain cortex and cis-pQTL of NECTIN2 in CSF. Overexpression of NECTIN2 led to an increase of sTREM2 supporting the genetic findings. To our knowledge, this is the largest study to date aimed at identifying genetic modifiers of CSF sTREM2. This study provided novel insights into the MS4A and TREM2 loci, two well-known AD risk genes, and identified TGFBR2 and NECTIN2 as additional modulators involved in TREM2 biology.
Gender-based violence in the context of armed conflict in Northern Ethiopia
Authors: Tewabe Desalew Salew , Azage Muluken , Wubetu Gizachew Yismaw , Fenta Sisay Awoke , Worke Mulugeta Dile , Asres Amanu Mekonen , Getnet Wallelign Alemnew , Kassie Genet Gedamu , Menber Yonatan , Munea Alemtsehay Mekonnen , Zeru Taye , Bekele Selamawit Alemayehu , Abdulahi Sadiya Osman , Adamne Tigist Biru , Belete Hiwot Debebe , Beyene Belay Bezabih , Abte Melkamu , Mersha Tesfaye B , Dadi Abel Fekadu , Enquobahrie Daniel A , Frissa Souci M. , Geda Yonas E.
Published: January 2024

Background

Gender-based violence (GBV) particularly against women is unfortunately common during armed conflicts. No rigorous and comprehensive empirical work has documented the extent of GBV and its consequences that took place during the two years of devastating armed conflict in Northern Ethiopia. This study aims to assess GBV and its consequences in war-torn areas of northern Ethiopia.

Methods

We used a qualitative method augmented by quantitative method to enroll research participants. We conducted in-depth interviews to characterize the lived experiences of GBV survivors. All interviews were conducted confidentially. The data were collected to the point of data saturation. All interviews were transcribed verbatim into local language, translated into English, and analyzed using a thematic analysis approach. We also used reports from healthcare facilities and conducted a descriptive analysis of the demographic characteristics of study participants.

Results

One thousand one hundred seventy-seven persons reported GBV to healthcare providers. The qualitative study identified several forms of violence (sexual, physical, and psychological). Gang rape against women including minors as young as 14 years old girls was reported. Additionally, the perpetrators sexually violated women who were pregnant, and elderly women as old as 65 years, who took refuge in religious institutions. The perpetrators committed direct assaults on the body with items (e.g., burning the body with cigarette fire) or weapons, holding women and girls as captives, and deprivation of sleep and food. GBV survivors reported stigma, prejudice, suicide attempts, nightmares, and hopelessness. GBV survivors dealt with the traumatic stress by outmigration (leaving their residences), seeking care at healthcare facilities, self-isolation, being silent, dropping out of school, and seeking counseling.

Conclusion

GBV survivors were subjected to multiple and compounding types of violence, with a wide range of adverse health consequences for survivors and their families. GBV survivors require multifaceted interventions including psychological, health, and economic support to rehabilitate them to lead a productive life.
Physical activity and mental health in school-aged children: a prospective two-wave study during the easing of the COVID-19 restrictions
Authors: Kopp Philipp M. , Möhler Eva , Gröpel Peter
Published: January 2024

Background

Because physical activity (PA) has many benefits for children’s and adolescents’ mental health, it has been suggested that PA may be an effective strategy to physically and mentally recover from the COVID-19 pandemic. This study tested the reciprocal relationship between PA and mental health during the easing of COVID-19 restrictions. It was hypothesized that mental health during the pandemic would determine how much children and adolescents re-engage in PA after easing the restrictions. Furthermore, it was hypothesized that PA engagement would predict mental health improvement after the pandemic.

Methods

This was a prospective study with two measurement occasions. Pretest data collection was undertaken in February 2022, shortly before German authorities eased and lifted the COVID-19 restrictions. The follow-up (posttest) occurred six weeks later (April 2022). Both times, a sample of elementary and grammar school students aged 6 to 18 years (N = 170) reported their mental health problems and health-related quality of life. Mental health problems were assessed with the Strengths and Difficulties Questionnaire and health-related quality of life was assessed with the KIDSCREEN-52 questionnaire. PA was measured continuously during the study period using smart electronic devices with a built-in pedometer.

Results

PA gradually increased after the easing of COVID-19 restrictions (p < .001). This increase was unrelated to pretest mental health problems and health-related quality of life except for emotional symptoms (p = .041). Participants with higher emotional symptoms showed a sharper increase in PA towards the end of the study period. Furthermore, hyperactivity decreased (p = .004) and physical well-being (p = .004), perceived autonomy (p < .001), and perceived quality of school environment (p = .008) improved from before to after the easing of restrictions, yet participants’ PA predicted none of these changes.

Conclusions

The adverse effects of COVID-19 containment on PA seem to alleviate after children and adolescents are allowed to return to schools. This is likely to be due to the school setting, which provides many different opportunities for formal and informal PA rather than students’ mental health. School-related PA programs should be part of children’s and adolescents’ recovery from the pandemic .
NK cell-triggered CCL5/IFNγ-CXCL9/10 axis underlies the clinical efficacy of neoadjuvant anti-HER2 antibodies in breast cancer
Authors: Santana-Hernández Sara , Suarez-Olmos Jesús , Servitja Sonia , Berenguer-Molins Pau , Costa-Garcia Marcel , Comerma Laura , Rea Anna , Perera-Bel Julia , Menendez Silvia , Arpí Oriol , Bermejo Begoña , Martínez María Teresa , Cejalvo Juan Miguel , Comino-Méndez Iñaki , Pascual Javier , Alba Emilio , López-Botet Miguel , Rojo Federico , Rovira Ana , Albanell Joan , Muntasell Aura
Published: January 2024

Background

The variability in responses to neoadjuvant treatment with anti-HER2 antibodies prompts to personalized clinical management and the development of innovative treatment strategies. Tumor-infiltrating Natural Killer (TI-NK) cells can predict the efficacy of HER2-targeted antibodies independently from clinicopathological factors in primary HER2-positive breast cancer patients. Understanding the mechanism/s underlying this association would contribute to optimizing patient stratification and provide the rationale for combinatorial approaches with immunotherapy.

Methods

We sought to uncover processes enriched in NK cell-infiltrated tumors as compared to NK cell-desert tumors by microarray analysis. Findings were validated in clinical trial-derived transcriptomic data. In vitro and in vivo preclinical models were used for mechanistic studies. Findings were analysed in clinical samples (tumor and serum) from breast cancer patients.

Results

NK cell-infiltrated tumors were enriched in CCL5/IFNG-CXCL9/10 transcripts. In multivariate logistic regression analysis, IFNG levels underlie the association between TI-NK cells and pathological complete response to neoadjuvant treatment with trastuzumab. Mechanistically, the production of IFN-ɣ by CD16+ NK cells triggered the secretion of CXCL9/10 from cancer cells. This effect was associated to tumor growth control and the conversion of CD16 into CD16-CD103+ NK cells in humanized in vivo models. In human breast tumors, the CD16 and CD103 markers identified lineage-related NK cell subpopulations capable of producing CCL5 and IFN-ɣ, which correlated with tissue-resident CD8+ T cells. Finally, an early increase in serum CCL5/CXCL9 levels identified patients with NK cell-rich tumors showing good responses to anti-HER2 antibody-based neoadjuvant treatment.

Conclusions

This study identifies specialized NK cell subsets as the source of IFN-ɣ influencing the clinical efficacy of anti-HER2 antibodies. It also reveals the potential of serum CCL5/CXCL9 as biomarkers for identifying patients with NK cell-rich tumors and favorable responses to anti-HER2 antibody-based neoadjuvant treatment.
Synthesis, design, biological evaluation, and computational analysis of some novel uracil-azole derivatives as cytotoxic agents
Authors: Emami Leila , Zare Fateme , Khabnadideh Soghra , Rezaei Zahra , Sabahi Zahra , Zare Gheshlaghi Saman , Behrouz Marzieh , Emami Mina , Ghobadi Zahra , Madadelahi Ardekani Sedighe , Barzegar Fatemeh , Ebrahimi Ali , Sabet Razieh
Published: January 2024

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil–azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure–activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil–azole hybrids can be considered as potential cytotoxic agents.
Quality of spirometry tests in the field of occupational health
Authors: Alavi Foumani Amirala , Alavi Foumani Seyyed Ali , Attarchi Mirsaeed , Etemadi Deilami Alireza , Majlesi Behzad , Ildari Shima , Eslami-Kenarsari Habib
Published: January 2024

Background

The spirometry test is a valuable test to evaluate the performance of the respiratory system. The interpretation of the results is highly dependent on the quality of its performance, while the inappropriate quality results in unwanted consequences for individuals and the healthcare system. This study investigated the quality of spirometry tests performed in occupational health.

Methods

In this cross-sectional study, the quality of 776 spirometry tests in different occupational centers by the specialists in Rasht, Iran, in 2020, based on the guidelines of the American Thoracic Society (ATS), was investigated. The quality and success rate of the test and the demographical characteristics of the operators and the participants were collected. All data was analyzed using SPSS software version 20.

Results

Out of 776 spirometry tests, about 69.7% were unacceptable. Among the unacceptable tests, a pause error between inhalation and exhalation was identified in 7.4% of tests. Additionally, 4.6% of the unacceptable tests exhibited a cough error within the first second, while an exhalation error of less than six was observed in 85%. Repeatability errors were found in 60.9% of the tests. Furthermore, among some errors, the communication error between the characteristics of the technicians and the test performance errors were evident.

Conclusion

According to the results, most of the performed tests were unacceptable with no repeatability, which indicated that the validity and quality of spirometry tests and their interpretation were inappropriate in the field of occupational health in Rasht, Iran.
High-fat Western diet alters crystalline silica-induced airway epithelium ion transport but not airway smooth muscle reactivity
Authors: Thompson Janet A. , Kashon Michael L. , McKinney Walter , Fedan Jeffrey S.
Published: January 2024

Objectives

Silicosis is an irreversible occupational lung disease resulting from crystalline silica inhalation. Previously, we discovered that Western diet (HFWD)-consumption increases susceptibility to silica-induced pulmonary inflammation and fibrosis. This study investigated the potential of HFWD to alter silica-induced effects on airway epithelial ion transport and smooth muscle reactivity.

Methods

Six-week-old male F344 rats were fed a HFWD or standard rat chow (STD) and exposed to silica (Min-U-Sil 5®, 15 mg/m3, 6 h/day, 5 days/week, for 39 d) or filtered air. Experimental endpoints were measured at 0, 4, and 8 weeks post-exposure. Transepithelial potential difference (Vt), short-circuit current (ISC) and transepithelial resistance (Rt) were measured in tracheal segments and ion transport inhibitors [amiloride, Na+ channel blocker; NPPB; Clˉ channel blocker; ouabain, Na+, K+-pump blocker] identified changes in ion transport pathways. Changes in airway smooth muscle reactivity to methacholine (MCh) were investigated in the isolated perfused trachea preparation.

Results

Silica reduced basal ISC at 4 weeks and HFWD reduced the ISC response to amiloride at 0 week compared to air control. HFWD + silica exposure induced changes in ion transport 0 and 4 weeks after treatment compared to silica or HFWD treatments alone. No effects on airway smooth muscle reactivity to MCh were observed.
MC180295 is a highly potent and selective CDK9 inhibitor with preclinical in vitro and in vivo efficacy in cancer
Authors: Zhang Hanghang , Huang Chen , Gordon John , Yu Sijia , Morton George , Childers Wayne , Abou-Gharbia Magid , Zhang Yi , Jelinek Jaroslav , Issa Jean-Pierre J.
Published: January 2024

Background

Inhibition of cyclin-dependent kinase 9 (CDK9), a novel epigenetic target in cancer, can reactivate epigenetically silenced genes in cancer by dephosphorylating the SWI/SNF chromatin remodeler BRG1. Here, we characterized the anti-tumor efficacy of MC180295, a newly developed CDK9 inhibitor.

Methods

In this study, we explored the pharmacokinetics of MC180295 in mice and rats, and tested the anti-tumor efficacy of MC180295, and its enantiomers, in multiple cancer cell lines and mouse models. We also combined CDK9 inhibition with a DNA methyltransferase (DNMT) inhibitor, decitabine, in multiple mouse models, and tested MC180295 dependence on T cells. Drug toxicity was measured by checking body weights and complete blood counts.

Results

MC180295 had high specificity for CDK9 and high potency against multiple neoplastic cell lines (median IC50 of 171 nM in 46 cell lines representing 6 different malignancies), with the highest potency seen in AML cell lines derived from patients with MLL translocations. MC180295 is a racemic mixture of two enantiomers, MC180379 and MC180380, with MC180380 showing higher potency in a live-cell epigenetic assay. Both MC180295 and MC180380 showed efficacy in in vivo AML and colon cancer xenograft models, and significant synergy with decitabine in both cancer models. Lastly, we found that CDK9 inhibition-mediated anti-tumoral effects were partially dependent on CD8 + T cells in vivo, indicating a significant immune component to the response.

Conclusions

MC180380, an inhibitor of cyclin-dependent kinase 9 (CDK9), is an efficacious anti-cancer agent worth advancing further toward clinical use.
TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy
Authors: Cai Chunyang , Gu Chufeng , He Shuai , Meng Chunren , Lai Dongwei , Zhang Jingfa , Qiu Qinghua
Published: January 2024

Background

Studies have shown that tet methylcytosine dioxygenase 2 (TET2) is highly expressed in diabetic retinopathy (DR), which reduces the DNA methylation of downstream gene promoters and activates the transcription. Abnormally expressed TET2 and downstream genes in a high-glucose environment are associated with retinal capillary leakage and neovascularization. Here, we investigated the downstream genes of TET2 and its potential association with neovascularization in proliferative diabetic retinopathy (PDR).

Methods

GSE60436, GSE57362, and GSE158333 datasets were analyzed to identify TET2-related hypomethylated and upregulated genes in PDR. Gene expression and promoter methylation of these genes under high glucose treatment were verified. Moreover, TET2 knockdown was used to assess its impact on tube formation and migration in human retinal microvascular endothelial cells (HRMECs), as well as its influence on downstream genes.

Results

Our analysis identified three key genes (PARVB, PTPRE, ECM1) that were closely associated with TET2 regulation. High glucose-treated HRMECs exhibited increased expression of TET2 and ECM1 while decreasing the promoter methylation level of ECM1. Subsequently, TET2 knockdown led to decreased migration ability and tube formation function of HRMECs. We further found a decreased expression of PARVB, PTPRE, and ECM1, accompanied by an increase in the promoter methylation of ECM1.

Conclusions

Our findings indicate the involvement of dysregulated TET2 expression in neovascularization by regulating the promoter methylation and transcription of downstream genes (notably ECM1), eventually leading to PDR. The TET2-induced hypomethylation of downstream gene promoters represents a potential therapeutic target and offers a novel perspective on the mechanism underlying neovascularization in PDR.

Graphical Abstract