bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of whole-body photobiomodulation on pain, quality of life, leisure physical activity, pain catastrophizing, kinesiophobia, and self-efficacy: a prospective randomized triple-blinded clinical trial with 6 months of follow-up
Authors: Navarro-Ledesma Santiago , Carroll James D. , González-Muñoz Ana , Burton Patricia
Published: January 2024

Background

The management of fibromyalgia (FM) symptoms on a global scale remains a complex endeavor. This study endeavors to assess the impact of whole-body photobiomodulation (PBM) compared to placebo PBM on pain, functionality, and psychological symptoms in individuals afflicted with fibromyalgia.

Objectives

The primary objectives of this research were to conduct a comparative analysis of the effects of whole-body photobiomodulation (PBM) and placebo PBM on pain, functionality, and psychological symptoms in patients suffering from fibromyalgia (FM).

Methods

A total of 42 subjects were recruited from a private care practice for participation in this triple-blinded, placebo-controlled, randomized clinical trial. Participants underwent 12 treatment sessions, and assessments were conducted at various intervals, including baseline (T0), midway through the 12-session treatment (T1), at the completion of the 12 sessions (T2), and follow-ups at 2 weeks (T3), 3 months (T4), and 6 months (T5).

Results

Statistical analysis revealed significant reductions in pain at T2, T3, and T5. Additionally, quality of life exhibited marked improvements after sessions at T1, T2, T3, T4, and T5. Leisure activity also demonstrated statistically significant improvements at T2, T3, T4, and T5. Furthermore, kinesiophobia showed significant differences between groups immediately after treatment at T2, T3, T4, and T5. Self-efficacy, when compared between groups, demonstrated significant differences at T3, T4, and T5 (two weeks after treatment). Lastly, pain catastrophizing exhibited significant differences only at T5.

Conclusion

The findings of this study indicate that whole-body PBM treatment for 4 weeks resulted in significant pain reduction and improved quality of life in individuals suffering from FM. Furthermore, kinesiophobia and self-efficacy demonstrated improvements in both short-term and long-term assessments, while pain catastrophizing showed improvement at the 6-month follow-up. Consequently, whole-body PBM emerges as a promising multifactorial treatment option for FM patients, though further studies are required to validate and strengthen these results.

Clinical Trial Registration:Clinicaltrials.gov, NCT0424897.
Association between obesity and age-related cataract: an updated systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Niazi Sana , Moshirfar Majid , Dastjerdi Mohammad H. , Niazi Feizollah , Doroodgar Farideh , Ambrósio Renato
Published: January 2024

Objective

There are inconsistent findings on the association between obesity and age-related cataract (ARC). This systematic review was done to summarize available findings on the association between obesity [defined by body mass index (BMI)] and ARC by performing a dose–response meta-analysis on eligible prospective cohort studies.

Methods

We performed a systematic search in PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until June 2022 to identify eligible publications.

Results

In total, 16 studies with a total sample size of 1,607,125 participants were included. Among all of these studies, there were 103,897 cases of ARC. In the follow-up periods ranging between 4 and 28 years, 4,870 cases of nuclear cataract, 1,611 cases of cortical cataract, and 1,603 cases of posterior subcapsular cataracts (PSC) were detected. By comparing the highest and lowest categories of BMI, we found that higher BMI was associated with an increased risk of ARC (RR: 1.18, 95% CI: 1.09–1.28) and PSC (RR: 1.44, 95% CI: 1.08–1.90). In the dose–response analysis, each 5 kg/m2 increase in BMI was associated with a 6 and 27% increased risk of ARC (RR: 1.06, 95% CI: 1.01–1.12) and PSC (RR: 1.27, 95% CI: 1.14–1.41), respectively. In addition, we found a positive association for cortical cataract among high-quality studies, in which higher BMI was associated with a 20% increased risk of cortical cataract (RR: 1.20, 95% CI: 1.02–1.42). In terms of nuclear cataract, we found no significant association either in the comparison between the highest and lowest categories of BMI or in the dose–response meta-analysis.

Conclusion

Obesity (defined by BMI) was associated with an increased risk of ARC, PSC, and cortical cataract in adults. However, such a positive association was not seen for nuclear cataract.

PROSPERO registration

CRD42022357132.
Case report: Good response to CMOP regimen containing mitoxantrone hydrochloride liposome (PLM60) as induction chemotherapy in patients with angioimmunoblastic T-cell lymphoma
Authors: Liang Lijie , Jiang Ming
Published: January 2024

Angioimmunoblastic T-cell lymphoma (AITL) is a highly aggressive subtype of peripheral T-cell lymphoma. The current prognosis with the first-line standard of care remains unsatisfactory, necessitating the exploration of more effective treatment options. We reported 5 cases of AITL receiving CMOP (mitoxantrone hydrochloride liposome, cyclophosphamide, vincristine, and prednisone). Cases 1 and 2 initially received CHOP as first-line induction therapy but switched to CMOP due to inadequate efficacy and cardiac adverse events. Cases 3, 4, and 5 were newly diagnosed and received CMOP. All patients achieved complete remission with acceptable cardiotoxicities and hematologic toxicities. After study treatment discontinuation, Cases 1 and 3 underwent autologous stem cell transplantation, and Cases 4 and 5 received oral maintenance agents. At the last follow-up, 4 patients remained in remission and 1 (Case 2) exhibited tumor recurrence. CMOP showed promise as a potential treatment option for AITL patients. Further research is essential to identify its efficacy and safety.
Efficacy of chemo-immunotherapy in metastatic BRAF-mutated lung cancer: a single-center retrospective data
Authors: Yan Ningning , Zhang Huixian , Guo Sanxing , Zhang Ziheng , Xu Yingchun , Xu Liang , Li Xingya
Published: January 2024

Background

The effectiveness of combining immune checkpoint inhibitors (ICIs) with chemotherapy in treating non-small cell lung cancers (NSCLCs) with BRAF mutations has not been sufficiently explored.

Methods

We compiled data from 306 NSCLC patients with identified BRAF mutations. We looked at efficacy by assessing the objective response rate (ORR) and disease control rate (DCR), as well as survival through measuring progression-free survival (PFS) and overall survival (OS).

Results

Out of the patient pool, 44 were treated with a regimen of immune-chemotherapy. Patients undergoing ICI in combination with chemotherapy had a median PFS of 4 months, and the median OS was recorded at 29 months. There was a notable increase in OS in patients receiving first-line treatment versus subsequent lines (29 vs 9.75 months, p=0.01); however, this was not the case with PFS (9 vs 4 months, p=0.46). The ORR for patients on ICIs was 36.3%. PFS and OS rates did not significantly differ between patients with the BRAF-V600E mutation and those with non-V600E mutations (p=0.75 and p=0.97, respectively). Additionally, we found a significant variation in PD-L1 expression between those who responded to treatment and those who didn’t (p=0.04).

Conclusion

Our findings indicate that chemo-immunotherapy as an initial treatment may lead to improved OS in patients with BRAF-mutated NSCLC when compared to its use in subsequent lines of therapy. Further studies are needed to validate these results and to delve deeper into how specific types of BRAF mutations and PD-L1 expression levels might predict a patient’s response to treatments in NSCLC.
Optimizing the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels
Authors: Hu Ke , He Su-Mei , Zhang Cun , Zhang Yi-Jia , Gu Qian , Shi Hao-Zhe , Wang Dong-Dong
Published: January 2024

Background

The appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels.

Methods

The present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.

Results

Within normal hematocrit levels, for children with lung transplantation who do not carry the CYP3A5*1 gene and have no coadministration with voriconazole, it is recommended to administer tacrolimus at a dosage of 0.02 mg/kg/day, divided into two doses, for children weighing 10–32 kg, and a dosage of 0.03 mg/kg/day, also divided into two doses, for children weighing 32–40 kg. For children with lung transplantation who carry the CYP3A5*1 gene and have no coadministration with voriconazole, tacrolimus dosages of 0.02, 0.03, and 0.04 mg/kg/day split into two doses are recommended for children weighing 10–15, 15–32, and 32–40 kg, respectively. For children with lung transplantation who do not carry the CYP3A5*1 gene and have coadministration with voriconazole, tacrolimus dosages of 0.01 and 0.02 mg/kg/day split into two doses are recommended for children weighing 10–17 and 17–40 kg, respectively. For children with lung transplantation who carry the CYP3A5*1 gene and have coadministration with voriconazole, a tacrolimus dosage of 0.02 mg/kg/day split into two doses is recommended for children weighing 10–40 kg.

Conclusions

It is the first time to optimize the initial dosage of tacrolimus in Chinese children undergoing lung transplantation within normal hematocrit.
Predicting preterm birth using auto-ML frameworks: a large observational study using electronic inpatient discharge data
Authors: Kong Deming , Tao Ye , Xiao Haiyan , Xiong Huini , Wei Weizhong , Cai Miao
Published: January 2024

Background

To develop and compare different AutoML frameworks and machine learning models to predict premature birth.

Methods

The study used a large electronic medical record database to include 715,962 participants who had the principal diagnosis code of childbirth. Three Automatic Machine Learning (AutoML) were used to construct machine learning models including tree-based models, ensembled models, and deep neural networks on the training sample (N = 536,971). The area under the curve (AUC) and training times were used to assess the performance of the prediction models, and feature importance was computed via permutation-shuffling.

Results

The H2O AutoML framework had the highest median AUC of 0.846, followed by AutoGluon (median AUC: 0.840) and Auto-sklearn (median AUC: 0.820), and the median training time was the lowest for H2O AutoML (0.14 min), followed by AutoGluon (0.16 min) and Auto-sklearn (4.33 min). Among different types of machine learning models, the Gradient Boosting Machines (GBM) or Extreme Gradient Boosting (XGBoost), stacked ensemble, and random forrest models had better predictive performance, with median AUC scores being 0.846, 0.846, and 0.842, respectively. Important features related to preterm birth included premature rupture of membrane (PROM), incompetent cervix, occupation, and preeclampsia.

Conclusions

Our study highlights the potential of machine learning models in predicting the risk of preterm birth using readily available electronic medical record data, which have significant implications for improving prenatal care and outcomes.
Molecular marker identification, antioxidant, antinociceptive, and anti-inflammatory responsiveness of malonic acid capped silver nanoparticle
Authors: Fatima Tehrim , Abrar Hina , Jahan Noor , Shamim Sana , Ahmed Nazia , Ali Asma Basharat , Begum Irshad , Ahmed Waqas
Published: January 2024

Nano-sized silver has drawn a great deal of attention in the field of health sciences owing to its remarkable therapeutic applications. Interestingly, the method applied to synthesize nanoparticles and the choice of reagents considerably influence their therapeutic potential and toxicities. Current research has explored the toxicity, anti-inflammatory, antinociceptive, and antioxidant responses of the malonic acid-capped silver nanoparticles (MA-AgNPs (C) by using sodium borohydride as a reducing agent at low temperatures by employing both in vitro and in vivo approaches. Furthermore, it has highlighted the synergistic effect of these novel compounds with conventional anti-inflammatory therapeutic agents. Acute and sub-acute toxicity analysis performed following OECD guidelines showed that the studied MA-AgNPs (C) are safer, and prominent toxic signs have not been detected at the highest studied dose of 2,000 mg/kg. Cytotoxicity evaluation through brine shrimp lethality revealed 20% lethality at the highest concentration of 169.8 μg/mL. Significantly, positive anti-inflammatory and analgesic responses alone as well as synergism with the standard were identified through in vitro as well as in vivo methods which were more potent at a lower dose (200 mg/kg). Notably synergistic outcomes were more pronounced than individual ones, indicating their prominent effect as a feasible drug delivery system. IL-6 and TNF-α assessment in excised paw tissue through RTPCR technique further supported their anti-inflammatory potential. DPPH assay revealed eminent in vitro antioxidant activity which was further corroborated by in vivo antioxidant assessment through evaluation of SOD in excised paw tissue.
Quercetin suppresses ROS production and migration by specifically targeting Rac1 activation in gliomas
Authors: Baba Rafia A. , Mir Hilal A. , Mokhdomi Taseem A. , Bhat Hina F. , Ahmad Ajaz , Khanday Firdous A.
Published: January 2024

P66Shc and Rac1 proteins are responsible for tumor-associated inflammation, particularly in brain tumors characterized by elevated oxidative stress and increased reactive oxygen species (ROS) production. Quercetin, a natural polyphenolic flavonoid, is a well-known redox modulator with anticancer properties. It has the capacity to cross the blood–brain barrier and, thus, could be a possible drug against brain tumors. In this study, we explored the effect of quercetin on Rac1/p66Shc-mediated tumor cell inflammation, which is the principal pathway for the generation of ROS in brain cells. Glioma cells transfected with Rac1, p66Shc, or both were treated with varying concentrations of quercetin for different time points. Quercetin significantly reduced the viability and migration of cells in an ROS-dependent manner with the concomitant inhibition of Rac1/p66Shc expression and ROS production in naïve and Rac1/p66Shc-transfected cell lines, suggestive of preventing Rac1 activation. Through molecular docking simulations, we observed that quercetin showed the best binding compared to other known Rac1 inhibitors and specifically blocked the GTP-binding site in the A-loop of Rac1 to prevent GTP binding and, thus, Rac1 activation. We conclude that quercetin exerts its anticancer effects via the modulation of Rac1-p66Shc signaling by specifically inhibiting Rac1 activation, thus restraining the production of ROS and tumor growth.
Crop modeling suggests limited transpiration would increase yield of sorghum across drought-prone regions of the United States
Authors: Raymundo Rubí , Mclean Greg , Sexton-Bowser Sarah , Lipka Alexander E. , Morris Geoffrey P.
Published: January 2024

Breeding sorghum to withstand droughts is pivotal to secure crop production in regions vulnerable to water scarcity. Limited transpiration (LT) restricts water demand at high vapor pressure deficit, saving water for use in critical periods later in the growing season. Here we evaluated the hypothesis that LT would increase sorghum grain yield in the United States. We used a process-based crop model, APSIM, which simulates interactions of genotype, environment, and management (G × E × M). In this study, the G component includes the LT trait (GT) and maturity group (GM), the EW component entails water deficit patterns, and the MP component represents different planting dates. Simulations were conducted over 33 years (1986-2018) for representative locations across the US sorghum belt (Kansas, Texas, and Colorado) for three planting dates and maturity groups. The interaction of GT x EW indicated a higher impact of LT sorghum on grain for late drought (LD), mid-season drought (MD), and early drought (ED, 8%), than on well-watered (WW) environments (4%). Thus, significant impacts of LT can be achieved in western regions of the sorghum belt. The lack of interaction of GT × GM × MP suggested that an LT sorghum would increase yield by around 8% across maturity groups and planting dates. Otherwise, the interaction GM × MP revealed that specific combinations are better suited across geographical regions. Overall, the findings suggest that breeding for LT would increase sorghum yield in the drought-prone areas of the US without tradeoffs.
An update on evolutionary, structural, and functional studies of receptor-like kinases in plants
Authors: Liu Jing , Li Wenjuan , Wu Guang , Ali Khawar
Published: January 2024

All living organisms must develop mechanisms to cope with and adapt to new environments. The transition of plants from aquatic to terrestrial environment provided new opportunities for them to exploit additional resources but made them vulnerable to harsh and ever-changing conditions. As such, the transmembrane receptor-like kinases (RLKs) have been extensively duplicated and expanded in land plants, increasing the number of RLKs in the advanced angiosperms, thus becoming one of the largest protein families in eukaryotes. The basic structure of the RLKs consists of a variable extracellular domain (ECD), a transmembrane domain (TM), and a conserved kinase domain (KD). Their variable ECDs can perceive various kinds of ligands that activate the conserved KD through a series of auto- and trans-phosphorylation events, allowing the KDs to keep the conserved kinase activities as a molecular switch that stabilizes their intracellular signaling cascades, possibly maintaining cellular homeostasis as their advantages in different environmental conditions. The RLK signaling mechanisms may require a coreceptor and other interactors, which ultimately leads to the control of various functions of growth and development, fertilization, and immunity. Therefore, the identification of new signaling mechanisms might offer a unique insight into the regulatory mechanism of RLKs in plant development and adaptations. Here, we give an overview update of recent advances in RLKs and their signaling mechanisms.
Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials
Authors: Cai Wenting , Zhang Ruobin , Yao Yao , Wu Qiuhui , Zhang Jinping
Published: January 2024

Objective

To systematically evaluate the efficacy and safety of a new hypoglycemic drug, tirzepatide, for treating obesity based on indicators such as BMI, waist circumference, and body weight.

Methods

A search formula was written using search terms such as “tirzepatide,” “overweight,” and “obesity.” A comprehensive search was conducted on databases such as PubMed, Cochrane Library, Embase, and Web of Science using a computer. Random controlled trial (RCT) literature was selected based on inclusion and exclusion criteria. After extracting the data, literature bias risk assessment and meta-analysis were conducted using RevMan 5.4 software. The search deadline is from the establishment of each database to May 2023.

Results

A total of 12 randomized controlled trials were included, with a total of 11,758 patients. Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = −1.71, 95% CI (−2.46, −0.95), p < 0.00001], [MD = −3.99, 95% CI (−3.69, −2.45), p < 0.00001], [MD = −4.02, 95% CI (−4.72, −3.31), p < 00.00001]. In terms of decreasing waist circumference, tirzepatide has a more significant advantage [MD = −4.08, 95% CI (−5.77, −2.39), p < 0.00001], [MD = −7.71, 95% CI (−10.17, −5.25), p < 0.00001], [MD = −9.15, 95% CI (−10.02, −8.29), p < 0.00001]. In the analysis of body weight, tirzepatide showed a more significant reduction effect compared to the control group [MD = −5.65, 95% CI (−7.47, −3.82), p < 0.001], [MD = −10.06, 95% CI (−12.86, −7.25), p < 0.001], [MD = −10.63, 95% CI (−12.42, −8.84), p < 0.001]. In comparison with placebo, tirzepatide had a prominent advantage in weight loss ≥20% and ≥25% [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001], [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]. Subgroup analysis showed a dose-dependent therapeutic effect. In terms of safety, compared with the placebo and insulin groups, the incidence of gastrointestinal adverse reactions was markedly higher in the tirzepatide group, slightly higher to the GLP-1 RAs group. The hypoglycemic (<70 mg/dL) risk of tirzepatide was slightly higher to that of placebo and GLP-1 RAs, but significantly lower than that of the insulin group [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]. The incidence of other adverse events, including pancreatitis, cholecystitis, major adverse cardiovascular events-4, hypersensitivity reactions, and neoplasms did not show significant statistical differences compared to the control group (p > 0.05).

Conclusion

Tirzepatide, as a weight loss drug, significantly reduces BMI, waist circumference and body weight while gastrointestinal adverse reactions need to be vigilant. Overall, its efficacy is significant and its safety is high.
Non-linear association of years of experience and burnout among nursing staff: a restricted cubic spline analysis
Authors: Liao Tanghong , Liu Yufei , Luo Wenqun , Duan Zhizhou , Zhan Kangmin , Lu Hongjian , Chen Xiangfan
Published: January 2024

Background

Occupational burnout is intricately linked to a spectrum of physical disorders encompassing respiratory, cardiovascular, and gastrointestinal conditions, as well as manifestations such as headaches, type 2 diabetes, elevated cholesterol levels, chronic fatigue, and muscle pain. Despite this association, there remains a paucity of research on the specific risk factors contributing to burnout among nurses in China.

Methods

This cross-sectional study utilized convenience sampling to recruit participants, with data analyzed from 1,774 nurse staffs. Psychosocial traits were assessed using the Three-Item Loneliness Scale for loneliness, the Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety symptoms, the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, the Connor Davidson Resilience Scale–10 item (CDRISC-10) for resilience, and the Maslach Burnout Inventory-Human Service Survey (MBI-HSS) for burn out. Restrictive cubic spline analysis to investigate the dose-response relationship between years of experience and burn out. Multivariate linear regression was employed to investigate the relationship between burnout and various risk factors.

Results

After controlling for basic demographic variables, good sleep quality was associated with a reduction in emotional exhaustion (β = −0.307, p < 0.001), while loneliness (β = 1.334, p < 0.001), depressive symptoms (β = 0.896, p < 0.001), and anxiety symptoms (β = 0.504, p < 0.001) were significantly associated with increased emotional exhaustion. Moreover, higher levels of resilience were positively associated with personal accomplishment (β = 0.635, p < 0.001). Regarding depersonalization, loneliness (β = 0.577, p < 0.001), depressive symptoms (β = 0.429, p < 0.001), and anxiety symptoms (β = 0.152, p < 0.01) were found to increase its level. Conversely, good resilience was associated with a decrease in depersonalization (β = −0.069, p < 0.001). The non-liner association between year of experience and emotional exhaustion was significantly (p < 0.05).

Conclusion

Our findings revealed that significant risk factors contributing to burnout among nursing staff including bad sleep quality, loneliness, lower level of resilience, anxiety symptoms, depressive symptoms. Moreover, a nonlinear correlation between years of experience and the likelihood of experiencing emotional exhaustion was exist.
Lower limb biomechanics of fully trained exoskeleton users reveal complex mechanisms behind the reductions in energy cost with human-in-the-loop optimization
Authors: Poggensee Katherine L. , Collins Steven H.
Published: January 2024

Exoskeletons that assist in ankle plantarflexion can improve energy economy in locomotion. Characterizing the joint-level mechanisms behind these reductions in energy cost can lead to a better understanding of how people interact with these devices, as well as to improved device design and training protocols. We examined the biomechanical responses to exoskeleton assistance in exoskeleton users trained with a lengthened protocol. Kinematics at unassisted joints were generally unchanged by assistance, which has been observed in other ankle exoskeleton studies. Peak plantarflexion angle increased with plantarflexion assistance, which led to increased total and biological mechanical power despite decreases in biological joint torque and whole-body net metabolic energy cost. Ankle plantarflexor activity also decreased with assistance. Muscles that act about unassisted joints also increased activity for large levels of assistance, and this response should be investigated over long-term use to prevent overuse injuries.
Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients
Authors: Abdel-Karim Tasneem R. , Hodges James S. , Herold Kevan C. , Pruett Timothy L. , Ramanathan Karthik V. , Hering Bernhard J. , Dunn Ty B. , Kirchner Varvara A. , Beilman Gregory J. , Bellin Melena D.
Published: January 2024

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.
Convolutional Neural Networks in the Diagnosis of Colon Adenocarcinoma
Authors: Leo Marco , Carcagnì Pierluigi , Signore Luca , Corcione Francesco , Benincasa Giulio , Laukkanen Mikko O. , Distante Cosimo
Published: January 2024

Colorectal cancer is one of the most lethal cancers because of late diagnosis and challenges in the selection of therapy options. The histopathological diagnosis of colon adenocarcinoma is hindered by poor reproducibility and a lack of standard examination protocols required for appropriate treatment decisions. In the current study, using state-of-the-art approaches on benchmark datasets, we analyzed different architectures and ensembling strategies to develop the most efficient network combinations to improve binary and ternary classification. We propose an innovative two-stage pipeline approach to diagnose colon adenocarcinoma grading from histological images in a similar manner to a pathologist. The glandular regions were first segmented by a transformer architecture with subsequent classification using a convolutional neural network (CNN) ensemble, which markedly improved the learning efficiency and shortened the learning time. Moreover, we prepared and published a dataset for clinical validation of the developed artificial neural network, which suggested the discovery of novel histological phenotypic alterations in adenocarcinoma sections that could have prognostic value. Therefore, AI could markedly improve the reproducibility, efficiency, and accuracy of colon cancer diagnosis, which are required for precision medicine to personalize the treatment of cancer patients.
Meropenem plus Ertapenem and Ceftazidime–Avibactam plus Aztreonam for the Treatment of Ventilator Associated Pneumonia Caused by Pan-Drug Resistant Klebsiella pneumonia
Authors: Mantzarlis Konstantinos , Manoulakas Efstratios , Parisi Kyriaki , Sdroulia Evaggelia , Zapaniotis Nikolaos , Tsolaki Vassiliki , Zakynthinos Epaminondas , Makris Demosthenes
Published: January 2024

Introduction: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. Results: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ–AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. Materials and methods: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime–avibactam plus aztreonam (CAZ–AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. Conclusions: Treatment with CAZ–AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings.
Computational Study of Abdominal Aortic Aneurysm Walls Accounting for Patient-Specific Non-Uniform Intraluminal Thrombus Thickness and Distinct Material Models: A Pre- and Post-Rupture Case
Authors: Sarantides Platon , Raptis Anastasios , Mathioulakis Dimitrios , Moulakakis Konstantinos , Kakisis John , Manopoulos Christos
Published: January 2024

An intraluminal thrombus (ILT) is present in the majority of abdominal aortic aneurysms, playing a crucial role in their growth and rupture. Although most computational studies do not include the ILT, in the present study, this is taken into account, laying out the whole simulation procedure, namely, from computed tomography scans to medical image segmentation, geometry reconstruction, mesh generation, biomaterial modeling, finite element analysis, and post-processing, all carried out in open software. By processing the tomography scans of a patient’s aneurysm before and after rupture, digital twins are reconstructed assuming a uniform aortic wall thickness. The ILT and the aortic wall are assigned different biomaterial models; namely, the first is modeled as an isotropic linear elastic material, and the second is modeled as the Mooney–Rivlin hyperelastic material as well as the transversely isotropic hyperelastic Holzapfel–Gasser–Ogden nonlinear material. The implementation of the latter requires the designation of local Cartesian coordinate systems in the aortic wall, suitably oriented in space, for the proper orientation of the collagen fibers. The composite aneurysm geometries (ILT and aortic wall structures) are loaded with normal and hypertensive static intraluminal pressure. Based on the calculated stress and strain distributions, ILT seems to be protecting the aneurysm from a structural point of view, as the highest stresses appear in the thrombus-free areas of the aneurysmal wall.
Bioprinting of Hydrogel-Based Drug Delivery Systems for Nerve Tissue Regeneration
Authors: Steele Eliza Marie , Carr Zacheus L. , Dosmar Emily
Published: January 2024

Globally, thousands of people are affected by severe nerve injuries or neurodegenerative disorders. These conditions cannot always be cured because nerve tissue either does not regenerate or does so at a slow rate. Therefore, tissue engineering has emerged as a potential treatment approach. This review discusses 3D bioprinting for scaffold manufacturing, highlights the advantages and disadvantages of common bioprinting techniques, describes important considerations for bioinks, biomaterial inks, and scaffolds, and discusses some drug delivery systems. The primary goal of this review is to bring attention to recent advances in nerve tissue engineering and its possible clinical applications in peripheral nerve, spinal cord, and cerebral nerve regeneration. Only studies that use 3D bioprinting or 3D printing to manufacture hydrogel scaffolds and incorporate the sustained release of a drug or growth factor for nerve regeneration are included. This review indicates that 3D printing is a fast and precise scaffold manufacturing technique but requires printing materials with specific properties to be effective in nervous tissue applications. The results indicate that the sustained release of certain drugs and growth factors from scaffolds can significantly improve post-printing cell viability, cell proliferation, adhesion, and differentiation, as well as functional recovery compared with scaffolds alone. However, more in vivo research needs to be conducted before this approach can be used in clinical applications.
Suggesting Dictyostelium as a Model for Disease-Related Protein Studies through Myosin II Polymerization Pathway
Authors: Liu Xiong , Shu Shi
Published: January 2024

Dictyostelium myosin II displays remarkable dynamism within the cell, continually undergoing polymerization and depolymerization processes. Under low-ion conditions, it assumes a folded structure like muscle myosins and forms thick filaments through polymerization. In our study, we presented intermediate structures observed during the early stages of polymerization of purified myosin via negative staining electron microscopy, immediately crosslinked with glutaraldehyde at the onset of polymerization. We identified folded monomers, dimers, and tetramers in the process. Our findings suggest that Dictyostelium myosin II follows a polymerization pathway in vitro akin to muscle myosin, with folded monomers forming folded parallel and antiparallel dimers that subsequently associate to create folded tetramers. These folded tetramers eventually unfold and associate with other tetramers to produce long filaments. Furthermore, our research revealed that ATP influences filament size, reducing it regardless of the status of RLC phosphorylation while significantly increasing the critical polymerization concentrations from 0.2 to 9 nM. In addition, we demonstrate the morphology of fully matured Dictyostelium myosin II filaments.
Temperature Matters: Enhancing Performance and Stability of Perovskite Solar Cells through Advanced Annealing Methods
Authors: Wu Shengcong , Li Chi , Lien Shui Yang , Gao Peng
Published: January 2024

Perovskite solar cells (PSCs) have garnered significant attention in the photovoltaic field owing to their exceptional photoelectric properties, including high light absorption, extensive carrier diffusion distance, and an adjustable band gap. Temperature is a crucial factor influencing both the preparation and performance of perovskite solar cells. The annealing temperature exerts a pronounced impact on the device structure, while the operational temperature influences carrier transport, perovskite band gap, and interface properties. This paper provides a comprehensive review of the influence of varied annealing temperatures on the hole transport layer, electron transport layer, and perovskite layer. Additionally, we present an overview of innovative annealing methods applied to perovskite materials. The effects of diverse working temperatures on the overall performance of perovskite cells are thoroughly examined and discussed in this review. In the end, different temperature conditions under ISOS testing conditions are summarized.
Online Measurement of Sodium Nitrite Based on Near-Infrared Spectroscopy
Authors: Xu Xianzhe , Zhang Yongshen , Zhang Mingmin , Li Dingming , Zuo Chen
Published: January 2024

In this study, a method was developed for the rapid online measurement of sodium nitrite solutions using near-infrared spectroscopy. A series of standard solutions of sodium nitrite at different concentrations were prepared, and the samples were measured in cuvettes and flow cells. Following the preprocessing of raw spectra and band selection, partial least squares were used to establish a prediction model, and the coefficient of determination (R2) of the validation set and the root mean square error of prediction (RMSEP) of the model were 0.9989 and 0.0338. The results demonstrate that the established model can meet the demands of online measurement and perform the rapid, nondestructive detection of sodium nitrite solutions, which provides some basis for the automated formulation of feedstock in spent fuel reprocessing.
A Pathway towards Climate Services for the Agricultural Sector
Authors: Charalampopoulos Ioannis , Droulia Fotoula
Published: January 2024

Climate change is already having a negative impact on many areas of human activity, affecting life globally. It is more urgent than ever to increase our adaptive capacity to respond to current and future climate change risks. Climate services refer to a specialized sector that encompasses both research and operational activities. This sector is primarily focused on interpreting and communicating knowledge and information about climate risks in a manner that is tailored to meet the specific needs of diverse user communities. Climate services offer a range of specialized outputs, including forecasts, assessments, and advisories, which enable users to make decisions that are based on an understanding of the potential impacts of climate change. The outputs of climate services are designed to help diverse user communities effectively manage risks and capitalize on opportunities arising from climate variability and change. An attempt is made to outline the fundamental elements of climate services and point out their contribution to various aspects of human activity, focusing on their essential role in the adaptability of the priority for action agricultural sector, which appears as considerably vulnerable to the change of considerably susceptible to climate conditions. This article is structured to answer basic questions about climate services in general and to show the specificities of climate services in the agricultural sector.
The Mexican Balsam, Impatiens mexicana Rydb: A Redescription Based on Morphological and Phylogenetic Studies, with an Update of the Current Geographical Range of the Species
Authors: Monzalvo René , Escorcia-Guerrero Diana Lizbeth , García-Montes Mario Adolfo , Rewicz Agnieszka , Rewicz Tomasz , Manríquez-Morán Norma L.
Published: January 2024

Impatiens mexicana is a native balsam restricted to the cloud forests of central and southwest Mexico, which is currently known to exist in four states (Zacatecas, Veracruz, Puebla, and Oaxaca), and is probably threatened by geographic restriction. Morphological and distributional information about this species is still scarce, with only a couple of investigations since its first description in 1910, which means the phylogenetic position of this species has yet to be placed. In order to contribute to knowledge of I. mexicana, morphological and molecular studies were carried out with material collected in the localities of Hidalgo, Veracruz, and Oaxaca, during expeditions from July to October 2021 and in 2022. The specimens selected were measured, photographed, and compared with morphological information from the six American balsams. At the same time, phylogenetic studies were carried out by using two regions of the cpDNA and one of the nrDNA. We report I. mexicana for the first time in Hidalgo state, and identify new registers in the Veracruz and Oaxaca localities, thus increasing the knowledge in its geographic distribution. We also redescribe the Mexican balsam by using new and complementary traits: we note that while the species is morphologically similar to I. capensis, it is distinguished by differences in flower color, the distribution of spot patterns on the upper petal, lower sepal, and lateral petals, and geographic information such as endemic geographic distribution in Mexico’s Tropical Montane Cloud Forest (TMCF). We also carried out phylogenetic analyses by using ITS and ITS + atpb-rbcL, which showed the Mexican balsam was independent from its Asian-American congeners. Interestingly, our genetic distance analyses reveal differences of 0.01–0.16% between I. mexicana and the other North American congeners that use ITS, atpb-rbcL and trnL-F, both independently and as concatenated genes: this low divergence most likely occurred because of the recent diversification of the group. However, both future redescriptions and phylogenetic studies in American species are imperative, as this will enable better discrimination.
De Novo Genome Assembly of the Sea Star Patiria pectinifera (Muller & Troschel, 1842) Using Oxford Nanopore Technology and Illumina Platforms
Authors: Rhee Jae-Sung , Nam Sang-Eun , Lee Seung Jae , Park Hyun
Published: January 2024

The sea star Patiria pectinifera (Asteroidea; Asterinidae; homotypic synonym: Asterina pectinifera; Muller & Troschel, 1842) is widely distributed in the coastal regions of the Seas of East Asia and the northern Pacific Ocean. Here, a de novo genome sequence of P. pectinifera as a reference for fundamental and applied research was constructed by employing a combination of long-read Oxford Nanopore Technology (ONT) PromethION, short-read Illumina platforms, and 10 × Genomics. The draft genome of P. pectinifera, containing 13,848,344 and 156,878,348 contigs from ONT and Illumina platforms, respectively, was obtained. Assembly with CANU resulted in 2262 contigs with an N50 length of 367 kb. Finally, ARCS + LINKS assembly combined these contigs into 328 scaffolds, totaling 499 Mb with an N50 length of 2 Mbp. The estimated genome size by GenomeScope analysis was 461 Mb. BUSCO analysis indicated that 930 (97.5%) of the expected genes were found in the assembly, with 889 (93.2%) being single-copy and 41 (4.3%) duplicated after searching against the metazoan database. Annotation, utilizing sequences obtained from Illumina RNA-Seq and Pacific Biosciences Iso-Seq, led to the identification of 22,367 protein-coding genes. When examining the orthologous relationship of P. pectinifera against the scaffolds of the common sea star Patiria miniata, high contiguity was observed. Annotation of repeat elements highlighted an enrichment of 1,121,079 transposable elements, constituting 47% of the genome, suggesting their potential role in shaping the genome structure of P. pectinifera. This de novo genome assembly is expected to be a valuable resource for future studies, providing insight into the developmental, environmental, and ecological aspects of P. pectinifera biology.
Linking QKD Testbeds across Europe
Authors: Brauer Max , Vicente Rafael J. , Buruaga Jaime S. , Méndez Rubén B. , Braun Ralf-Peter , Geitz Marc , Rydlichkowski Piotr , Brunner Hans H. , Fung Fred , Peev Momtchil , Pastor Antonio , Lopez Diego R. , Martin Vicente , Brito Juan P.
Published: January 2024

Quantum-key-distribution (QKD) networks are gaining importance and it has become necessary to analyze the most appropriate methods for their long-distance interconnection. In this paper, four different methods of interconnecting remote QKD networks are proposed. The methods are used to link three different QKD testbeds in Europe, located in Berlin, Madrid, and Poznan. Although long-distance QKD links are only emulated, the methods used can serve as a blueprint for the secure interconnection of distant QKD networks in the future. Specifically, the presented approaches combine, in a transparent way, different fiber and satellite physical media, as well as common standards of key delivery interfaces. The testbed interconnections are designed to increase the security by utilizing multipath techniques and multiple hybridizations of QKD and post-quantum cryptography (PQC) algorithms.
Agreeing to Stop: Reliable Latency-Adaptive Decision Making via Ensembles of Spiking Neural Networks
Authors: Chen Jiechen , Park Sangwoo , Simeone Osvaldo
Published: January 2024

Spiking neural networks (SNNs) are recurrent models that can leverage sparsity in input time series to efficiently carry out tasks such as classification. Additional efficiency gains can be obtained if decisions are taken as early as possible as a function of the complexity of the input time series. The decision on when to stop inference and produce a decision must rely on an estimate of the current accuracy of the decision. Prior work demonstrated the use of conformal prediction (CP) as a principled way to quantify uncertainty and support adaptive-latency decisions in SNNs. In this paper, we propose to enhance the uncertainty quantification capabilities of SNNs by implementing ensemble models for the purpose of improving the reliability of stopping decisions. Intuitively, an ensemble of multiple models can decide when to stop more reliably by selecting times at which most models agree that the current accuracy level is sufficient. The proposed method relies on different forms of information pooling from ensemble models and offers theoretical reliability guarantees. We specifically show that variational inference-based ensembles with p-variable pooling significantly reduce the average latency of state-of-the-art methods while maintaining reliability guarantees.